Skip to main content
SpringerLink
Log in

Developmental Disorders of the Cerebellum and Neurotrophic Factors

  • Chapter
  • First Online:
Development of the Cerebellum from Molecular Aspects to Diseases

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

  • 424 Accesses

Abstract

The cerebellum plays a central role in motor control and cognition features such as attention. Thus, a disturbance in cerebellar development results in neurological disorders such as attention deficit hyperactivity disorder (ADHD), congenital ataxia, and autism. The role of neurotrophic factors on the growth, proliferation, differentiation, and arborization of neurons and thus neurodevelopmental disorders has been established and investigated for decades. Numerous studies have shown changes in the level of a neurotrophic factor in the serum or tissue and alterations in their receptors and components of their signaling pathways in these neurodevelopmental diseases. This chapter provides a brief overview of neurotrophic factors and their role in cerebellar development. We also focus on the functions of the neurotrophin system in developmental disorders and diseases of the cerebellum.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Abbeduto LS, Ozonoff A, Thurman JA, McDuffie J, Schweitzer HR, Yudofsky S, Robert W. Neurodevelopmental disorders. In: Textbook of psychiatry. 6th ed. Arlington: The American Psychiatric Publishing; 2015.

    Google Scholar 

  2. Abe Y, Honsho M, Itoh R, Kawaguchi R, Fujitani M, Fujiwara K, Hirokane M, Matsuzaki T, Nakayama K, Ohgi R, Marutani T, Nakayama KI, Yamashita T, Fujiki Y. Peroxisome biogenesis deficiency attenuates the BDNF-TrkB pathway-mediated development of the cerebellum. Life Sci Alliance. 2018;1(6):e201800062.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Adamaszek M, D’Agata F, Ferrucci R, Habas C, Keulen S, Kirkby KC, Leggio M, Mariën P, Molinari M, Moulton E, Orsi L, Van Overwalle F, Papadelis C, Priori A, Sacchetti B, Schutter DJ, Styliadis C, Verhoeven J. Consensus paper: cerebellum and emotion. Cerebellum. 2017;16(2):552–76.

    Article  CAS  PubMed  Google Scholar 

  4. Alleva E, Cirulli F, Calamandrei G, Rondinini C, Capirci O, Aloe L, Volterra V. Williams syndrome. Ann Ist Super Sanita. 1999;35(2):211–9.

    CAS  PubMed  Google Scholar 

  5. Aloe L, Iannitelli A, Angelucci F, Bersani G, Fiore M. Studies in animal models and humans suggesting a role of nerve growth factor in schizophrenia-like disorders. Behav Pharmacol. 2000;11(3–4):235–42.

    Article  CAS  PubMed  Google Scholar 

  6. Angelucci F, Ricci V, Pomponi M, Conte G, Mathe AA, Tonali PA, Bria P. Chronic heroin and cocaine abuse is associated with decreased serum concentrations of the nerve growth factor and brain-derived neurotrophic factor. J Psychopharmacol. 2007;21(8):820–5.

    Article  CAS  PubMed  Google Scholar 

  7. Angelucci F, De Bartolo P, Gelfo F, Foti F, Cutuli D, Bossu P, Caltagirone C, Petrosini L. Increased concentrations of nerve growth factor and brain-derived neurotrophic factor in the rat cerebellum after exposure to environmental enrichment. Cerebellum. 2009;8(4):499–506.

    Article  CAS  PubMed  Google Scholar 

  8. Antonelli A, Lenzi L, Nakagawara A, Osaki T, Chiaretti A, Aloe L. Tumor suppressor proteins are differentially affected in human ependymoblastoma and medulloblastoma cells exposed to nerve growth factor. Cancer Investig. 2007;25(2):94–101.

    Article  CAS  Google Scholar 

  9. Aref D, Moffatt CJ, Agnihotri S, Ramaswamy V, Dubuc AM, Northcott PA, Taylor MD, Perry A, Olson JM, Eberhart CG, Croul SE. Canonical TGF-beta pathway activity is a predictor of SHH-driven medulloblastoma survival and delineates putative precursors in cerebellar development. Brain Pathol. 2013;23(2):178–91.

    Article  CAS  PubMed  Google Scholar 

  10. Aruga J, Millen KJ. ZIC1 function in normal cerebellar development and human developmental pathology. Adv Exp Med Biol. 2018;1046:249–68.

    Article  CAS  PubMed  Google Scholar 

  11. Aureli A, Del Beato T, Sebastiani P, Marimpietri A, Melillo CV, Sechi E, Di Loreto S. Attention-deficit hyperactivity disorder and intellectual disability: a study of association with brain-derived neurotrophic factor gene polymorphisms. Int J Immunopathol Pharmacol. 2010;23(3):873–80.

    Article  CAS  PubMed  Google Scholar 

  12. Banaschewski T, Becker K, Scherag S, Franke B, Coghill D. Molecular genetics of attention-deficit/hyperactivity disorder: an overview. Eur Child Adolesc Psychiatry. 2010;19(3):237–57.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Barbosa AG, Pratesi R, Paz GSC, Dos Santos M, Uenishi RH, Nakano EY, Gandolfi L, Pratesi CB. Assessment of BDNF serum levels as a diagnostic marker in children with autism spectrum disorder. Sci Rep. 2020;10(1):17348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Battaglia A. Sensory impairment in mental retardation: a potential role for NGF. Arch Ital Biol. 2011;149(2):193–203.

    PubMed  Google Scholar 

  15. Becker A, Grecksch G, Schwegler H, Roskoden T. Expression of mRNA of neurotrophic factors and their receptors are significantly altered after subchronic ketamine treatment. Med Chem. 2008;4(3):256–63.

    Article  CAS  PubMed  Google Scholar 

  16. Beckinghausen J, Sillitoe RV. Insights into cerebellar development and connectivity. Neurosci Lett. 2019;688:2–13.

    Article  CAS  PubMed  Google Scholar 

  17. Ben-Shachar S, Chahrour M, Thaller C, Shaw CA, Zoghbi HY. Mouse models of MeCP2 disorders share gene expression changes in the cerebellum and hypothalamus. Hum Mol Genet. 2009;18(13):2431–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Berger-Sweeney J. Cognitive deficits in Rett syndrome: what we know and what we need to know to treat them. Neurobiol Learn Mem. 2011;96(4):637–46.

    Article  CAS  PubMed  Google Scholar 

  19. Bergman O, Westberg L, Lichtenstein P, Eriksson E, Larsson H. Study on the possible association of brain-derived neurotrophic factor polymorphism with the developmental course of symptoms of attention deficit and hyperactivity. Int J Neuropsychopharmacol. 2011;14(10):1367–76.

    Article  CAS  PubMed  Google Scholar 

  20. Bickford PC, Bowenkamp K, Taglialatela G, Hoertig G, Granholm AC. GDNF improves cerebellar Purkinje neuron function in aged F344 rats. Microsc Res Tech. 2001;54(5):309–16.

    Article  CAS  PubMed  Google Scholar 

  21. Bilgic A, Toker A, Isik U, Kilinc I. Serum brain-derived neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 levels in children with attention-deficit/hyperactivity disorder. Eur Child Adolesc Psychiatry. 2016;26(3):355–63.

    Article  PubMed  Google Scholar 

  22. Borghesani PR, Peyrin JM, Klein R, Rubin J, Carter AR, Schwartz PM, Luster A, Corfas G, Segal RA. BDNF stimulates migration of cerebellar granule cells. Development. 2002;129(6):1435–42.

    Article  CAS  PubMed  Google Scholar 

  23. Calamandrei G, Alleva E, Cirulli F, Queyras A, Volterra V, Capirci O, Vicari S, Giannotti A, Turrini P, Aloe L. Serum NGF levels in children and adolescents with either Williams syndrome or Down syndrome. Develop Med Child Neurol. 2000;42(11):746–50.

    Article  CAS  PubMed  Google Scholar 

  24. Calamandrei G, Aloe L, Hajek J, Zappella M. Developmental profile of serum nerve growth factor levels in Rett complex. Ann Ist Super Sanita. 2001;37(4):601–5.

    CAS  PubMed  Google Scholar 

  25. Cao BB, Zhang XX, Du CY, Liu Z, Qiu YH, Peng YP. TGF-β1 provides neuroprotection via inhibition of microglial activation in 3-Acetylpyridine-induced cerebellar ataxia model rats. Front Neurosci. 2020;14:187.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J, Zoghbi HY. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science. 2008;320(5880):1224–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Chaste P, Leboyer M. Autism risk factors: genes, environment, and gene-environment interactions. Dialogues Clin Neurosci. 2012;14(3):281–92.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Chen S, Charness ME. Ethanol disrupts axon outgrowth stimulated by netrin-1, GDNF, and L1 by blocking their convergent activation of Src family kinase signaling. J Neurochem. 2012;123(4):602–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Cho SC, Kim HW, Kim BN, Kim JW, Shin MS, Chung S, Cho DY, Jung SW, Yoo HJ, Chung IW, Chung US, Son JW. Gender-specific association of the brain-derived neurotrophic factor gene with attention-deficit/hyperactivity disorder. Psychiatry Investig. 2010;7(4):285–90.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Choo M, Miyazaki T, Yamazaki M, Kawamura M, Nakazawa T, Zhang J, Tanimura A, Uesaka N, Watanabe M, Sakimura K, Kano M. Retrograde BDNF to TrkB signaling promotes synapse elimination in the developing cerebellum. Nat Commun. 2017;8(1):195.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Chou TT, Trojanowski JQ, Lee VM. A novel apoptotic pathway induced by nerve growth factor-mediated TrkA activation in medulloblastoma. J Biol Chem. 2000;275(1):565–70.

    Article  CAS  PubMed  Google Scholar 

  32. Co M, Anderson AG, Konopka G. FOXP transcription factors in vertebrate brain development, function, and disorders. Wiley Interdiscip Rev Dev Biol. 2020;9(5):e375.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cohen-Cory S, Dreyfus CF, Black IB. Expression of high- and low-affinity nerve growth factor receptors by Purkinje cells in the developing rat cerebellum. Exp Neurol. 1989;105(1):104–9.

    Article  CAS  PubMed  Google Scholar 

  34. Copf T. Impairments in dendrite morphogenesis as etiology for neurodevelopmental disorders and implications for therapeutic treatments. Neurosci Biobehav Rev. 2016;68:946–78.

    Article  PubMed  Google Scholar 

  35. Corominas-Roso M, Ramos-Quiroga JA, Ribases M, Sanchez-Mora C, Palomar G, Valero S, Bosch R, Casas M. Decreased serum levels of brain-derived neurotrophic factor in adults with attention-deficit hyperactivity disorder. Int J Neuropsychopharmacol. 2013;16(6):1267–75.

    Article  CAS  PubMed  Google Scholar 

  36. Costa B, Kean MJ, Ast V, Knight JD, Mett A, Levy Z, Ceccarelli DF, Badillo BG, Eils R, Konig R, Gingras AC, Fainzilber M. STK25 protein mediates TrkA and CCM2 protein-dependent death in pediatric tumor cells of neural origin. J Biol Chem. 2012;287(35):29285–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Courchesne E, Pramparo T, Gazestani VH, Lombardo MV. The ASD living biology: from cell proliferation to clinical phenotype. Mol Psychiatry. 2019;24(1):88–107.

    Article  PubMed  Google Scholar 

  38. Crews FT, Nixon K. Mechanisms of neurodegeneration and regeneration in alcoholism. Alcohol Alcohol. 2009;44(2):115–27.

    Article  CAS  PubMed  Google Scholar 

  39. Damarjian TG, Craner MJ, Black JA, Waxman SG. Upregulation and colocalization of p75 and Nav1.8 in Purkinje neurons in experimental autoimmune encephalomyelitis. Neurosci Lett. 2004;369(3):186–90.

    Article  CAS  PubMed  Google Scholar 

  40. Das UN. Autism as a disorder of deficiency of brain-derived neurotrophic factor and altered metabolism of polyunsaturated fatty acids. Nutrition. 2013;29(10):1175–85.

    Article  CAS  PubMed  Google Scholar 

  41. Davis MI. Ethanol-BDNF interactions: still more questions than answers. Pharmacol Ther. 2008;118(1):36–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Desmond JE, Fiez JA. Neuroimaging studies of the cerebellum: language, learning and memory. Trends Cogn Sci. 1998;2(9):355–62.

    Article  CAS  PubMed  Google Scholar 

  43. Dohrman DP, West JR, Pantazis NJ. Ethanol reduces expression of the nerve growth factor receptor, but not nerve growth factor protein levels in the neonatal rat cerebellum. Alcohol Clin Exp Res. 1997;21(5):882–93.

    Article  CAS  PubMed  Google Scholar 

  44. Ebendal T. Function and evolution in the NGF family and its receptors. J Neurosci Res. 1992;32(4):461–70.

    Article  CAS  PubMed  Google Scholar 

  45. Edgin JO, Clark CAC, Massand E, Karmiloff-Smith A. Building an adaptive brain across development: targets for neurorehabilitation must begin in infancy. Front Behav Neurosci. 2015;9:1662–5153. (Electronic)).

    Article  Google Scholar 

  46. Fatemi SH, Folsom TD, Rooney RJ, Thuras PD. Expression of GABAA alpha2-, beta1- and epsilon-receptors are altered significantly in the lateral cerebellum of subjects with schizophrenia, major depression and bipolar disorder. Transl Psychiatry. 2013;3:e303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Fatemi SH, Folsom TD, Liesch SB, Kneeland RE, Karkhane Yousefi M, Thuras PD. The effects of prenatal H1N1 infection at E16 on FMRP, glutamate, GABA, and reelin signaling systems in developing murine cerebellum. J Neurosci Res. 2017;95(5):1110–22.

    Article  CAS  PubMed  Google Scholar 

  48. Fauchais AL, Lalloue F, Lise MC, Boumediene A, Preud’homme JL, Vidal E, Jauberteau MO. Role of endogenous brain-derived neurotrophic factor and sortilin in B cell survival. J Immunol. 2008;181(5):3027–38.

    Article  CAS  PubMed  Google Scholar 

  49. Firozan B, Goudarzi I, Elahdadi Salmani M, Lashkarbolouki T, Rezaei A, Abrari K. Estradiol increases expression of the brain-derived neurotrophic factor after acute administration of ethanol in the neonatal rat cerebellum. Eur J Pharmacol. 2014;732:1–11.

    Article  CAS  PubMed  Google Scholar 

  50. Fletcher JL, Murray SS, Xiao J. Brain-derived neurotrophic factor in central nervous system myelination: a new mechanism to promote myelin plasticity and repair. Int J Mol Sci. 2018;19(12):4131.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Flores-Dorantes MT, Díaz-López YE, Gutiérrez-Aguilar R. Environment and Gene Association with obesity and their impact on neurodegenerative and neurodevelopmental diseases. Front Neurosci. 2020;14:863.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Florez-McClure ML, Linseman DA, Chu CT, Barker PA, Bouchard RJ, Le SS, Laessig TA, Heidenreich KA. The p75 neurotrophin receptor can induce autophagy and death of cerebellar Purkinje neurons. J Neurosci. 2004;24(19):4498–509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Fu F, Li Y, Li R, Lei TY, Wang D, Yang X, Han J, Pan M, Zhen L, Ou YM, Li J, Li FT, Jing XY, Li DZ, Liao C. NDUFA4 enhances neuron growth by triggering growth factors and inhibiting neuron apoptosis through Bcl-2 and cytochrome C mediated signaling pathway. Am J Transl Res. 2018;10(1):164–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Fuentealba CR, Fiedler JL, Peralta FA, Avalos AM, Aguayo FI, Morgado-Gallardo KP, Aliaga EE. Region-specific reduction of BDNF protein and transcripts in the hippocampus of juvenile rats prenatally treated with sodium valproate. Front Mol Neurosci. 2019;12:261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Fumagalli F, Moro F, Caffino L, Orru A, Cassina C, Giannotti G, Di Clemente A, Racagni G, Riva MA, Cervo L. Region-specific effects on BDNF expression after contingent or non-contingent cocaine i.v. self-administration in rats. Int J Neuropsychopharmacol. 2013;16(4):913–8.

    Article  CAS  PubMed  Google Scholar 

  56. Galvez-Contreras AY, Campos-Ordonez T, Gonzalez-Castaneda RE, Gonzalez-Perez O. Alterations of growth factors in autism and attention-deficit/hyperactivity disorder. Front Psych. 2017;8:126.

    Article  Google Scholar 

  57. Gate D, Danielpour M, Rodriguez J Jr, Kim GB, Levy R, Bannykh S, Breunig JJ, Kaech SM, Flavell RA, Town T. T-cell TGF-beta signaling abrogation restricts medulloblastoma progression. Proc Natl Acad Sci U S A. 2014;111(33):E3458–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ge Y, Belcher SM, Light KE. Alterations of cerebellar mRNA specific for BDNF, p75NTR, and TrkB receptor isoforms occur within hours of ethanol administration to 4-day-old rat pups. Brain Res Dev Brain Res. 2004;151(1–2):99–109.

    Article  CAS  PubMed  Google Scholar 

  59. Gelfo F, Cutuli D, Foti F, Laricchiuta D, De Bartolo P, Caltagirone C, Petrosini L, Angelucci F. Enriched environment improves motor function and increases neurotrophins in hemicerebellar lesioned rats. Neurorehabil Neural Repair. 2011;25(3):243–52.

    Article  PubMed  Google Scholar 

  60. Gericke CA, Schulte-Herbruggen O, Arendt T, Hellweg R. Chronic alcohol intoxication in rats leads to a strong but transient increase in NGF levels in distinct brain regions. J Neural Transm (Vienna). 2006;113(7):813–20.

    Article  CAS  PubMed  Google Scholar 

  61. Ghiretti AE, Paradis S. Molecular mechanisms of activity-dependent changes in dendritic morphology: role of RGK proteins. Trends Neurosci. 2014;37(7):399–407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Gill JS, Sillitoe RV. Functional outcomes of cerebellar malformations. Front Cell Neurosci. 2019;13:441.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Glickstein M, Strata P, Voogd J. Cerebellum: history. Neuroscience. 2009;162(3):549–59.

    Article  CAS  PubMed  Google Scholar 

  64. Gomes FC, Sousa Vde O, Romao L. Emerging roles for TGF-beta1 in nervous system development. Int J Dev Neurosci. 2005;23(5):413–24.

    Article  CAS  PubMed  Google Scholar 

  65. Gonzalez-Burgos I, Alejandre-Gomez M. Cerebellar granule cell and Bergmann glial cell maturation in the rat is disrupted by pre- and post-natal exposure to moderate levels of ethanol. Int J Dev Neurosci. 2005;23(4):383–8.

    Article  CAS  PubMed  Google Scholar 

  66. Good JM, Mahoney M, Miyazaki T, Tanaka KF, Sakimura K, Watanabe M, Kitamura K, Kano M. Maturation of cerebellar Purkinje cell population activity during postnatal refinement of climbing Fiber network. Cell Rep. 2017;21(8):2066–73.

    Article  CAS  PubMed  Google Scholar 

  67. Guney E, Ceylan MF, Kara M, Tekin N, Goker Z, Senses Dinc G, Ozturk O, Eker S, Kizilgun M. Serum nerve growth factor (NGF) levels in children with attention deficit/hyperactivity disorder (ADHD). Neurosci Lett. 2014;560(1872–7972 (Electronic)):107–11.

    Article  CAS  PubMed  Google Scholar 

  68. Haldipur P, Dang D, Aldinger KA, Janson OK, Guimiot F, Adle-Biasette H, Dobyns WB, Siebert JR, Russo R, Millen KJ. Phenotypic outcomes in mouse and human Foxc1 dependent Dandy-Walker cerebellar malformation suggest shared mechanisms. elife. 2017;6:e20898.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Halepoto DM, Bashir S, Al-Ayadhi L. Possible role of brain-derived neurotrophic factor (BDNF) in autism spectrum disorder: current status. J Coll Physicians Surg Pak. 2014;24(4):274–8.

    PubMed  Google Scholar 

  70. Hampson DR, Blatt GJ. Autism spectrum disorders and neuropathology of the cerebellum. Front Neurosci. 2015;9(1662–4548 (Print)):420.

    PubMed  PubMed Central  Google Scholar 

  71. Harper C. The neuropathology of alcohol-specific brain damage, or does alcohol damage the brain? J Neuropathol Exp Neurol. 1998;57(2):101–10.

    Article  CAS  PubMed  Google Scholar 

  72. Hawi Z, Cummins TD, Tong J, Arcos-Burgos M, Zhao Q, Matthews N, Newman DP, Johnson B, Vance A, Heussler HS, Levy F, Easteal S, Wray NR, Kenny E, Morris D, Kent L, Gill M, Bellgrove MA. Rare DNA variants in the brain-derived neurotrophic factor gene increase risk for attention-deficit hyperactivity disorder: a next-generation sequencing study. Mol Psychiatry. 2016;22(4):580–4.

    Article  PubMed  Google Scholar 

  73. Heaton MB, Mitchell JJ, Paiva M. Ethanol-induced alterations in neurotrophin expression in developing cerebellum: relationship to periods of temporal susceptibility. Alcohol Clin Exp Res. 1999;23(10):1637–42.

    CAS  PubMed  Google Scholar 

  74. Heaton MB, Moore DB, Paiva M, Madorsky I, Mayer J, Shaw G. The role of neurotrophic factors, apoptosis-related proteins, and endogenous antioxidants in the differential temporal vulnerability of neonatal cerebellum to ethanol. Alcohol Clin Exp Res. 2003;27(4):657–69.

    Article  CAS  PubMed  Google Scholar 

  75. Heaton MB, Madorsky I, Paiva M, Siler-Marsiglio KI. Ethanol-induced reduction of neurotrophin secretion in neonatal rat cerebellar granule cells is mitigated by vitamin E. Neurosci Lett. 2004;370(1):51–4.

    Article  CAS  PubMed  Google Scholar 

  76. Hickey CL, Sherman JC, Goldenberg P, Kritzer A, Caruso P, Schmahmann JD, Colvin MK. Cerebellar cognitive affective syndrome: insights from Joubert syndrome. Cerebellum Ataxias. 2018;5:5.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Hill SY, Wang S, Carter H, Tessner K, Holmes B, McDermott M, Zezza N, Stiffler S. Cerebellum volume in high-risk offspring from multiplex alcohol dependence families: association with allelic variation in GABRA2 and BDNF. Psychiatry Res. 2011;194(3):304–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Hoffmann A, Spengler D. Chromatin Remodeling complex NuRD in neurodevelopment and neurodevelopmental disorders. Front Genet. 2019;10:682.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Ivry RB. Cerebellar involvement in clumsiness and other developmental disorders. Neural Plast. 2003;10(1–2):141–53.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Jockers-Scherubl MC, Rentzsch J, Danker-Hopfe H, Radzei N, Schurer F, Bahri S, Hellweg R. Adequate antipsychotic treatment normalizes serum nerve growth factor concentrations in schizophrenia with and without cannabis or additional substance abuse. Neurosci Lett. 2006;400(3):262–6.

    Article  PubMed  Google Scholar 

  81. Jones J, Jaramillo-Merchan J, Bueno C, Pastor D, Viso-Leon M, Martinez S. Mesenchymal stem cells rescue Purkinje cells and improve motor functions in a mouse model of cerebellar ataxia. Neurobiol Dis. 2010;40(2):415–23.

    Article  PubMed  Google Scholar 

  82. Kalinowska-Lyszczarz A, Losy J. The role of neurotrophins in multiple sclerosis-pathological and clinical implications. Int J Mol Sci. 2012;13(10):13713–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kalus I, Rohn S, Puvirajesinghe TM, Guimond SE, Eyckerman-Kolln PJ, Ten Dam G, van Kuppevelt TH, Turnbull JE, Dierks T. Sulf1 and Sulf2 differentially modulate Heparan Sulfate proteoglycan Sulfation during postnatal cerebellum development: evidence for neuroprotective and neurite outgrowth promoting functions. PLoS One. 2015;10(10):e0139853.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Kamath SP, Chen AI. Myocyte enhancer factor 2c regulates dendritic complexity and connectivity of cerebellar Purkinje cells. Mol Neurobiol. 2019;56(6):4102–19.

    Article  CAS  PubMed  Google Scholar 

  85. Kapfhammer JP. Cellular and molecular control of dendritic growth and development of cerebellar Purkinje cells. Prog Histochem Cytochem. 2004;39(3):131–82.

    Article  PubMed  Google Scholar 

  86. Kasah S, Oddy C, Basson MA. Autism-linked CHD gene expression patterns during development predict multi-organ disease phenotypes. J Anat. 2018;233(6):755–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Khan S. IGFBP-2 Signaling in the brain: from brain development to higher order brain functions. Front Endocrinol. 2019;10:822.

    Article  Google Scholar 

  88. Kirsten TB, Casarin RC. Pioglitazone abolishes cognition impairments as well as BDNF and neurotensin disturbances in a rat model of autism. Bio Open. 2019;8(5):bio041327.

    Article  CAS  Google Scholar 

  89. Koh S, Oyler GA, Higgins GA. Localization of nerve growth factor receptor messenger RNA and protein in the adult rat brain. Exp Neurol. 1989;106(3):209–21.

    Article  CAS  PubMed  Google Scholar 

  90. Kwon HJ, Ha M, Jin HJ, Hyun JK, Shim SH, Paik KC, Park WS, Lim MH. Association between BDNF gene polymorphisms and attention deficit hyperactivity disorder in Korean children. Genet Test Mol Biomarkers. 2015;19(7):366–71.

    Article  CAS  PubMed  Google Scholar 

  91. Laco MN, Oliveira CR, Paulson HL, Rego AC. Compromised mitochondrial complex II in models of Machado-Joseph disease. Biochim Biophys Acta. 2012;1822(2):139–49.

    Article  CAS  PubMed  Google Scholar 

  92. Lanktree M, Squassina A, Krinsky M, Strauss J, Jain U, Macciardi F, Kennedy JL, Muglia P. Association study of brain-derived neurotrophic factor (BDNF) and LIN-7 homolog (LIN-7) genes with adult attention-deficit/hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet. 2008;147b(6):945–51.

    Article  PubMed  Google Scholar 

  93. Larkfors L, Lindsay RM, Alderson RF. Characterization of the responses of Purkinje cells to neurotrophin treatment. J Neurochem. 1996;66(4):1362–73.

    Article  CAS  PubMed  Google Scholar 

  94. Le Duc D, Spataru A, Ceanga M, Zagrean L, Schoneberg T, Toescu EC, Zagrean AM. Developmental exposure to ethanol increases the neuronal vulnerability to oxygen-glucose deprivation in cerebellar granule cell cultures. Brain Res. 2015;1614:1–13.

    Article  PubMed  Google Scholar 

  95. Lee BH, Kim YK. Increased plasma brain-derived neurotropic factor, not nerve growth factor-Beta, in schizophrenia patients with better response to risperidone treatment. Neuropsychobiology. 2009;59(1):51–8.

    Article  CAS  PubMed  Google Scholar 

  96. Lewin GR. Neurotrophins and the specification of neuronal phenotype. Philos Trans R Soc Lond Ser B Biol Sci. 1996;351(1338):405–11.

    Article  CAS  Google Scholar 

  97. Lewin GR, Barde YA. Physiology of the neurotrophins. Annu Rev Neurosci. 1996;19:289–317.

    Article  CAS  PubMed  Google Scholar 

  98. Li Z, Ding M, Thiele CJ, Luo J. Ethanol inhibits brain-derived neurotrophic factor-mediated intracellular signaling and activator protein-1 activation in cerebellar granule neurons. Neuroscience. 2004;126(1):149–62.

    Article  CAS  PubMed  Google Scholar 

  99. Li C, Macdonald JI, Hryciw T, Meakin SO. Nerve growth factor activation of the TrkA receptor induces cell death, by macropinocytosis, in medulloblastoma Daoy cells. J Neurochem. 2010;112(4):882–99.

    Article  CAS  PubMed  Google Scholar 

  100. Light KE, Ge Y, Belcher SM. Early postnatal ethanol exposure selectively decreases BDNF and truncated TrkB-T2 receptor mRNA expression in the rat cerebellum. Brain Res Mol Brain Res. 2001;93(1):46–55.

    Article  CAS  PubMed  Google Scholar 

  101. Light KE, Belcher SM, Pierce DR. Time course and manner of Purkinje neuron death following a single ethanol exposure on postnatal day 4 in the developing rat. Neuroscience. 2002a;114(2):327–37.

    Article  CAS  PubMed  Google Scholar 

  102. Light KE, Brown DP, Newton BW, Belcher SM, Kane CJ. Ethanol-induced alterations of neurotrophin receptor expression on Purkinje cells in the neonatal rat cerebellum. Brain Res. 2002b;924(1):71–81.

    Article  CAS  PubMed  Google Scholar 

  103. Lindsay RM, Alderson RF, Friedman B, Hyman C, Ip NY, Furth ME, Maisonpierre PC, Squinto SP, Yancopoulos GD. The neurotrophin family of NGF-related neurotrophic factors. Restor Neurol Neurosci. 1991;2(4):211–20.

    CAS  PubMed  Google Scholar 

  104. Liu SH, Shi XJ, Fan FC, Cheng Y. Peripheral blood neurotrophic factor levels in children with autism spectrum disorder: a meta-analysis. Sci Rep. 2021;11(1):15.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Lombardi VC, De Meirleir KL, Subramanian K, Nourani SM, Dagda RK, Delaney SL, Palotás A. Nutritional modulation of the intestinal microbiota; future opportunities for the prevention and treatment of neuroimmune and neuroinflammatory disease. J Nutr Biochem. 2018;61:1–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Louie CM, Gleeson JG. Genetic basis of Joubert syndrome and related disorders of cerebellar development. Hum Mol Genet. 2005;14(2):R235–42.

    Article  CAS  PubMed  Google Scholar 

  107. Máčová L, Bičíková M, Ostatníková D, Hill M, Stárka L. Vitamin D, neurosteroids and autism. Physiol Res. 2017;66(Suppl 3):S333–s340.

    Article  PubMed  Google Scholar 

  108. Mahabir S, Chatterjee D, Misquitta K, Chatterjee D, Gerlai R. Lasting changes induced by mild alcohol exposure during embryonic development in BDNF, NCAM and synaptophysin-positive neurons quantified in adult zebrafish. Eur J Neurosci. 2018;47(12):1457–73.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Marchetti D, Mrak RE, Paulsen DD, Sinnappah-Kang ND. Neurotrophin receptors and heparanase: a functional axis in human medulloblastoma invasion. J Exp Clin Cancer Res. 2007;26(1):5–23.

    CAS  PubMed  Google Scholar 

  110. Mariën P, Ackermann H, Adamaszek M, Barwood CHS, Beaton A, Desmond J, De Witte E, Fawcett AJ, Hertrich I, Küper M, Leggio M, Marvel C, Molinari M, Murdoch BE, Nicolson RI, Schmahmann JD, Stoodley CJ, Thürling M, Timmann D, Wouters E, Ziegler W. Consensus paper: language and the cerebellum: an ongoing enigma. Cerebellum. 2014;13(3):386–410.

    PubMed  PubMed Central  Google Scholar 

  111. Marmolino D, Manto M. Past, present and future therapeutics for cerebellar ataxias. Curr Neuropharmacol. 2010;8(1):41–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Martinez-Cengotitabengoa, M., K. S. MacDowell, S. Alberich, F. J. Diaz, B. Garcia-Bueno, R. Rodriguez-Jimenez, M. Bioque, E. Berrocoso, M. Parellada, A. Lobo, P. A. Saiz, C. Matute, M. Bernardo, A. Gonzalez-Pinto, J. C. Leza and Flamm-Peps (2016). "BDNF and NGF signalling in early phases of psychosis: relationship with inflammation and response to antipsychotics after 1 year." Schizophr Bull 42(1): 142–151.

    Google Scholar 

  113. Martinotti G, Di Iorio G, Marini S, Ricci V, De Berardis D, Di Giannantonio M. Nerve growth factor and brain-derived neurotrophic factor concentrations in schizophrenia: a review. J Biol Regul Homeost Agents. 2012;26(3):347–56.

    CAS  PubMed  Google Scholar 

  114. McAlhany RE Jr, Miranda RC, Finnell RH, West JR. Ethanol decreases Glial-Derived Neurotrophic Factor (GDNF) protein release but not mRNA expression and increases GDNF-stimulated Shc phosphorylation in the developing cerebellum. Alcohol Clin Exp Res. 1999;23(10):1691–7.

    Article  CAS  PubMed  Google Scholar 

  115. McAlhany RE Jr, West JR, Miranda RC. Glial-derived neurotrophic factor (GDNF) prevents ethanol-induced apoptosis and JUN kinase phosphorylation. Brain Res Dev Brain Res. 2000;119(2):209–16.

    Article  CAS  PubMed  Google Scholar 

  116. Meis S, Endres T, Lessmann V. Neurotrophin signalling in amygdala-dependent cued fear learning. Cell Tissue Res. 2020;382(1):161–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Mellesmoen A, Sheeler C, Ferro A, Rainwater O, Cvetanovic M. Brain derived neurotrophic factor (BDNF) delays onset of pathogenesis in transgenic mouse model of spinocerebellar ataxia type 1 (SCA1). Front Cell Neurosci. 2018;12:509.

    Article  CAS  PubMed  Google Scholar 

  118. Millen KJ, Gleeson JG. Cerebellar development and disease. Curr Opin Neurobiol. 2008;18(1):12–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Mitoma H, Manto M, Shaikh AG. Mechanisms of ethanol-induced cerebellar ataxia: underpinnings of neuronal death in the cerebellum. Int J Environ Res Public Health. 2021;18(16)

    Google Scholar 

  120. Mizoguchi Y, Monji A. Microglial intracellular Ca(2+) Signaling in synaptic development and its alterations in neurodevelopmental disorders. Front Cell Neurosci. 2017;11:69.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Mizoguchi T, Shimazawa M, Ohuchi K, Kuse Y, Nakamura S, Hara H. Impaired cerebellar development in mice overexpressing VGF. Neurochem Res. 2019;44(2):374–87.

    Article  CAS  PubMed  Google Scholar 

  122. Moore DB, Walker DW, Heaton MB. Neonatal ethanol exposure alters bcl-2 family mRNA levels in the rat cerebellar vermis. Alcohol Clin Exp Res. 1999;23(7):1251–61.

    Article  CAS  PubMed  Google Scholar 

  123. Moore DB, Madorsky I, Paiva M, Barrow Heaton M. Ethanol exposure alters neurotrophin receptor expression in the rat central nervous system: effects of neonatal exposure. J Neurobiol. 2004;60(1):114–26.

    Article  CAS  PubMed  Google Scholar 

  124. Nelson PG, Kuddo T, Song EY, Dambrosia JM, Kohler S, Satyanarayana G, Vandunk C, Grether JK, Nelson KB. Selected neurotrophins, neuropeptides, and cytokines: developmental trajectory and concentrations in neonatal blood of children with autism or down syndrome. Int J Dev Neurosci. 2006;24(1):73–80.

    Article  CAS  PubMed  Google Scholar 

  125. Nickl-Jockschat T, Michel TM. The role of neurotrophic factors in autism. Mol Psychiatry. 2011;16(5):478–90.

    Article  CAS  PubMed  Google Scholar 

  126. Niitsu T, Iyo M, Hashimoto K. Sigma-1 receptor agonists as therapeutic drugs for cognitive impairment in neuropsychiatric diseases. Curr Pharm Des. 2012;18(7):875–83.

    Article  CAS  PubMed  Google Scholar 

  127. Ohrtman JD, Stancik EK, Lovinger DM, Davis MI. Ethanol inhibits brain-derived neurotrophic factor stimulation of extracellular signal-regulated/mitogen-activated protein kinase in cerebellar granule cells. Alcohol. 2006;39(1):29–37.

    Article  CAS  PubMed  Google Scholar 

  128. Ohta T, Watanabe T, Katayama Y, Kurihara J, Yoshino A, Nishimoto H, Kishimoto H. TrkA expression is associated with an elevated level of apoptosis in classic medulloblastomas. Neuropathology. 2006;26(3):170–7.

    Article  PubMed  Google Scholar 

  129. Osborne BF, Turano A, Caulfield JI, Schwarz JM. Sex- and region-specific differences in microglia phenotype and characterization of the peripheral immune response following early-life infection in neonatal male and female rats. Neurosci Lett. 2019;692:1–9.

    Article  PubMed  Google Scholar 

  130. Parikh V, Evans DR, Khan MM, Mahadik SP. Nerve growth factor in never-medicated first-episode psychotic and medicated chronic schizophrenic patients: possible implications for treatment outcome. Schizophr Res. 2003;60(2–3):117–23.

    Article  PubMed  Google Scholar 

  131. Parisi MA. The molecular genetics of Joubert syndrome and related ciliopathies: the challenges of genetic and phenotypic heterogeneity. Transl Sci Rare Dis. 2019;4(1–2):25–49.

    PubMed  PubMed Central  Google Scholar 

  132. Park H, Poo MM. Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci. 2013;14(1):7–23.

    Article  CAS  PubMed  Google Scholar 

  133. Park S, Kim BN, Kim JW, Jung YK, Lee J, Shin MS, Yoo HJ, Cho SC. The role of the brain-derived neurotrophic factor genotype and parenting in early life in predicting externalizing and internalizing symptoms in children with attention-deficit hyperactivity disorder. Behav Brain Funct. 2014;10:43.

    Article  PubMed  PubMed Central  Google Scholar 

  134. Pasquin S, Sharma M, Gauchat JF. Ciliary neurotrophic factor (CNTF): new facets of an old molecule for treating neurodegenerative and metabolic syndrome pathologies. Cytokine Growth Factor Rev. 2015;26(5):507–15.

    Article  CAS  PubMed  Google Scholar 

  135. Paz RD, Andreasen NC, Daoud SZ, Conley R, Roberts R, Bustillo J, Perrone-Bizzozero NI. Increased expression of activity-dependent genes in cerebellar glutamatergic neurons of patients with schizophrenia. Am J Psychiatry. 2006;163(10):1829–31.

    Article  PubMed  Google Scholar 

  136. Peddada S, Yasui DH, LaSalle JM. Inhibitors of differentiation (ID1, ID2, ID3 and ID4) genes are neuronal targets of MeCP2 that are elevated in Rett syndrome. Hum Mol Genet. 2006;15(12):2003–14.

    Article  CAS  PubMed  Google Scholar 

  137. Picard H, Amado I, Mouchet-Mages S, Olie JP, Krebs MO. The role of the cerebellum in schizophrenia: an update of clinical, cognitive, and functional evidences. Schizophr Bull. 2008;34(1):155–72.

    Article  PubMed  Google Scholar 

  138. Qiao X, Hefti F, Knusel B, Noebels JL. Selective failure of brain-derived neurotrophic factor mRNA expression in the cerebellum of stargazer, a mutant mouse with ataxia. J Neurosci. 1996;16(2):640–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Quartu M, Serra MP, Manca A, Follesa P, Lai ML, Del Fiacco M. Neurotrophin-like immunoreactivity in the human pre-term newborn, infant, and adult cerebellum. Int J Dev Neurosci. 2003;21(1):23–33.

    Article  CAS  PubMed  Google Scholar 

  140. Rahimi Balaei M, Jiao X, Ashtari N, Afsharinezhad P, Ghavami S, Marzban H. Cerebellar expression of the Neurotrophin receptor p75 in naked-ataxia mutant mouse. Int J Mol Sci. 2016;17(1)

    Google Scholar 

  141. Rahimi-Balaei M, Afsharinezhad P, Bailey K, Buchok M, Yeganeh B, Marzban H. Embryonic stages in cerebellar afferent development. Cerebellum Ataxias. 2015;2(2053–8871 (Electronic)):7.

    Article  PubMed  PubMed Central  Google Scholar 

  142. Rahman A, Weber J, Labin E, Lai C, Prieto AL. Developmental expression of Neuregulin-3 in the rat central nervous system. J Comp Neurol. 2019;527(4):797–817.

    Article  CAS  PubMed  Google Scholar 

  143. Riikonen R. Treatment of autistic spectrum disorder with insulin-like growth factors. Eur J Paediatr Neurol. 2016;20(6):816–23.

    Article  PubMed  Google Scholar 

  144. Roussa, E., O. von Bohlen und Halbach and K. Krieglstein (2009). "TGF-beta in dopamine neuron development, maintenance and neuroprotection." Adv Exp Med Biol 651: 81–90.

    Google Scholar 

  145. Roussel MF, Hatten ME. Cerebellum development and medulloblastoma. Curr Top Dev Biol. 2011;94:235–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Sadakata T, Furuichi T. Developmentally regulated Ca2+−dependent activator protein for secretion 2 (CAPS2) is involved in BDNF secretion and is associated with autism susceptibility. Cerebellum. 2009;8(3):312–22.

    Article  CAS  PubMed  Google Scholar 

  147. Sadakata T, Kakegawa W, Mizoguchi A, Washida M, Katoh-Semba R, Shutoh F, Okamoto T, Nakashima H, Kimura K, Tanaka M, Sekine Y, Itohara S, Yuzaki M, Nagao S, Furuichi T. Impaired cerebellar development and function in mice lacking CAPS2, a protein involved in neurotrophin release. J Neurosci. 2007;27(10):2472–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Sajdel-Sulkowska EM, Xu M, Koibuchi N. Cerebellar brain-derived neurotrophic factor, nerve growth factor, and Neurotrophin-3 expression in male and female rats is differentially affected by Hypergravity exposure during discrete developmental periods. Cerebellum. 2009a;8(4):454–62.

    Article  CAS  PubMed  Google Scholar 

  149. Sajdel-Sulkowska EM, Xu M, Koibuchi N. Increase in cerebellar neurotrophin-3 and oxidative stress markers in autism. Cerebellum. 2009b;8(3):366–72.

    Article  CAS  PubMed  Google Scholar 

  150. Sanchez-Mora C, Ribases M, Ramos-Quiroga JA, Casas M, Bosch R, Boreatti-Hummer A, Heine M, Jacob CP, Lesch KP, Fasmer OB, Knappskog PM, Kooij JJ, Kan C, Buitelaar JK, Mick E, Asherson P, Faraone SV, Franke B, Johansson S, Haavik J, Reif A, Bayes M, Cormand B. Meta-analysis of brain-derived neurotrophic factor p.Val66Met in adult ADHD in four European populations. Am J Med Genet B Neuropsychiatr Genet. 2010;153B(2):512–23.

    Article  CAS  PubMed  Google Scholar 

  151. Santucci D, Kawano F, Ohira T, Terada M, Nakai N, Francia N, Alleva E, Aloe L, Ochiai T, Cancedda R, Goto K, Ohira Y. Evaluation of gene, protein and neurotrophin expression in the brain of mice exposed to space environment for 91 days. PLoS One. 2012;7(7):e40112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Sariola H. The neurotrophic factors in non-neuronal tissues. Cell Mol Life Sci. 2001;58(8):1061–6.

    Article  CAS  PubMed  Google Scholar 

  153. Sarna JR, Hawkes R. Patterned Purkinje cell death in the cerebellum. Prog Neurobiol. 2003;70(6):473–507.

    Article  CAS  PubMed  Google Scholar 

  154. Sarter M, Gehring WJ, Kozak R. More attention must be paid: the neurobiology of attentional effort. Brain Res Rev. 2006;51(2):145–60.

    Article  PubMed  Google Scholar 

  155. Scassellati C, Zanardini R, Tiberti A, Pezzani M, Valenti V, Effedri P, Filippini E, Conte S, Ottolini A, Gennarelli M, Bocchio-Chiavetto L. Serum brain-derived neurotrophic factor (BDNF) levels in attention deficit-hyperactivity disorder (ADHD). Eur Child Adolesc Psychiatry. 2014;23(3):173–7.

    Article  PubMed  Google Scholar 

  156. Schaevitz LR, Moriuchi JM, Nag N, Mellot TJ, Berger-Sweeney J. Cognitive and social functions and growth factors in a mouse model of Rett syndrome. Physiol Behav. 2010;100(3):255–63.

    Article  CAS  PubMed  Google Scholar 

  157. Schmahmann JD. The cerebellum and cognition. Neurosci Lett. 2019;688:62–75.

    Article  CAS  PubMed  Google Scholar 

  158. Schmahmann JD, Caplan D. Cognition, emotion and the cerebellum. Brain. 2006;129(Pt 2):290–2.

    Article  PubMed  Google Scholar 

  159. Schuhmann B, Dietrich A, Sel S, Hahn C, Klingenspor M, Lommatzsch M, Gudermann T, Braun A, Renz H, Nockher WA. A role for brain-derived neurotrophic factor in B cell development. J Neuroimmunol. 2005;163(1–2):15–23.

    Article  CAS  PubMed  Google Scholar 

  160. Sergaki MC, López-Ramos JC, Stagkourakis S, Gruart A, Broberger C, Delgado-García JM, Ibáñez CF. Compromised survival of cerebellar molecular layer interneurons lacking GDNF receptors GFRα1 or RET impairs Normal cerebellar motor learning. Cell Rep. 2017;19(10):1977–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Serrano M. Epigenetic cerebellar diseases. Handb Clin Neurol. 2018;155:227–44.

    Article  PubMed  Google Scholar 

  162. Sheeler C, Rosa JG, Borgenheimer E, Mellesmoen A, Rainwater O, Cvetanovic M. Post-symptomatic delivery of brain-derived neurotrophic factor (BDNF) ameliorates spinocerebellar ataxia type 1 (SCA1) pathogenesis. Cerebellum. 2021;20(3):420–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Shevelkin AV, Ihenatu C, Pletnikov MV. Pre-clinical models of neurodevelopmental disorders: focus on the cerebellum. Rev Neurosci. 2014;25(2):177–94.

    Article  PubMed  PubMed Central  Google Scholar 

  164. Shim SH, Hwangbo Y, Kwon YJ, Jeong HY, Lee BH, Lee HJ, Kim YK. Increased levels of plasma brain-derived neurotrophic factor (BDNF) in children with attention deficit-hyperactivity disorder (ADHD). Prog Neuro-Psychopharmacol Biol Psychiatry. 2008;32(8):1824–8.

    Article  CAS  Google Scholar 

  165. Shim SH, Hwangbo Y, Yoon HJ, Kwon YJ, Lee HY, Hwang JA, Kim YK. Increased levels of plasma glial-derived neurotrophic factor in children with attention deficit hyperactivity disorder. Nord J Psychiatry. 2015;69(7):546–51.

    Article  PubMed  Google Scholar 

  166. Shojaei S, Ghavami S, Panjehshahin MR, Owji AA. Effects of ethanol on the expression level of various BDNF mRNA isoforms and their encoded protein in the hippocampus of adult and embryonic rats. Int J Mol Sci. 2015;16(12):30422–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Shoval G, Weizman A. The possible role of neurotrophins in the pathogenesis and therapy of schizophrenia. Eur Neuropsychopharmacol. 2005;15(3):319–29.

    Article  CAS  PubMed  Google Scholar 

  168. Stoodley CJ. The cerebellum and neurodevelopmental disorders. Cerebellum. 2016;15(1):34–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Stoodley CJ, Stein JF. Cerebellar function in developmental dyslexia. Cerebellum. 2013;12(2):267–76.

    Article  PubMed  Google Scholar 

  170. Subramaniam S, Strelau J, Unsicker K. GDNF prevents TGF-beta-induced damage of the plasma membrane in cerebellar granule neurons by suppressing activation of p38-MAPK via the phosphatidylinositol 3-kinase pathway. Cell Tissue Res. 2008;331(2):373–83.

    Article  CAS  PubMed  Google Scholar 

  171. Syed Z, Dudbridge F, Kent L. An investigation of the neurotrophic factor genes GDNF, NGF, and NT3 in susceptibility to ADHD. Am J Med Genet B Neuropsychiatr Genet. 2007;144B(3):375–8.

    Article  PubMed  Google Scholar 

  172. Takahashi M, Ishikawa K, Sato N, Obayashi M, Niimi Y, Ishiguro T, Yamada M, Toyoshima Y, Takahashi H, Kato T, Takao M, Murayama S, Mori O, Eishi Y, Mizusawa H. Reduced brain-derived neurotrophic factor (BDNF) mRNA expression and presence of BDNF-immunoreactive granules in the spinocerebellar ataxia type 6 (SCA6) cerebellum. Neuropathology. 2012;32(6):595–603.

    Article  PubMed  Google Scholar 

  173. Takata A, Miyake N, Tsurusaki Y, Fukai R, Miyatake S, Koshimizu E, Kushima I, Okada T, Morikawa M, Uno Y, Ishizuka K, Nakamura K, Tsujii M, Yoshikawa T, Toyota T, Okamoto N, Hiraki Y, Hashimoto R, Yasuda Y, Saitoh S, Ohashi K, Sakai Y, Ohga S, Hara T, Kato M, Nakamura K, Ito A, Seiwa C, Shirahata E, Osaka H, Matsumoto A, Takeshita S, Tohyama J, Saikusa T, Matsuishi T, Nakamura T, Tsuboi T, Kato T, Suzuki T, Saitsu H, Nakashima M, Mizuguchi T, Tanaka F, Mori N, Ozaki N, Matsumoto N. Integrative analyses of De novo mutations provide deeper biological insights into autism Spectrum disorder. Cell Rep. 2018;22(3):734–47.

    Article  CAS  PubMed  Google Scholar 

  174. Tan S, Wang RH, Niu HX, Shi CH, Mao CY, Zhang R, Song B, Sun SL, Liu XJ, Hou HM, Liu YT, Gao Y, Fang H, Kong XD, Xu YM. Nerve growth factor for the treatment of spinocerebellar ataxia type 3: an open-label study. Chin Med J. 2015;128(3):291–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Thomaz A, Pinheiro KDV, Souza BK, Gregianin L, Brunetto AL, Brunetto AT, de Farias CB, Jaeger MDC, Ramaswamy V, Nör C, Taylor MD, Roesler R. Antitumor activities and cellular changes induced by TrkB inhibition in Medulloblastoma. Front Pharmacol. 2019;10:698.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Thomaz A, Jaeger M, Brunetto AL, Brunetto AT, Gregianin L, de Farias CB, Ramaswamy V, Nör C, Taylor MD, Roesler R. Neurotrophin signaling in medulloblastoma. Cancers. 2020;12(9):2542.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Tojo H, Takami K, Kaisho Y, Nakata M, Abe T, Shiho O, Igarashi K. Neurotrophin-3 is expressed in the posterior lobe of mouse cerebellum, but does not affect the cerebellar development. Neurosci Lett. 1995;192(3):169–72.

    Article  CAS  PubMed  Google Scholar 

  178. Tolbert DL, Bradley MW, Tolod EG, Torres-Aleman I, Clark BR. Chronic intraventricular infusion of glial cell line-derived neurotrophic factor (GDNF) rescues some cerebellar Purkinje cells from heredodegeneration. Exp Neurol. 2001;170(2):375–9.

    Article  CAS  PubMed  Google Scholar 

  179. Tsai PT. Autism and cerebellar dysfunction: evidence from animal models. Semin Fetal Neonatal Med. 2016;21(5):349–55.

    Article  PubMed  Google Scholar 

  180. Unsicker K, Krieglstein K. TGF-betas and their roles in the regulation of neuron survival. Adv Exp Med Biol. 2002;513:353–74.

    Article  CAS  PubMed  Google Scholar 

  181. Valderrama X, Rapin N, Verge VM, Misra V. Zhangfei induces the expression of the nerve growth factor receptor, trkA, in medulloblastoma cells and causes their differentiation or apoptosis. J Neuro-Oncol. 2009;91(1):7–17.

    Article  CAS  Google Scholar 

  182. Varghese M, Keshav N, Jacot-Descombes S, Warda T, Wicinski B, Dickstein DL, Harony-Nicolas H, De Rubeis S, Drapeau E, Buxbaum JD, Hof PR. Autism spectrum disorder: neuropathology and animal models. Acta Neuropathol. 2017;134(4):537–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Vetreno RP, Hall JM, Savage LM. Alcohol-related amnesia and dementia: animal models have revealed the contributions of different etiological factors on neuropathology, neurochemical dysfunction and cognitive impairment. Neurobiol Learn Mem. 2011;96(4):596–608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Wan J, Steffen J, Yourshaw M, Mamsa H, Andersen E, Rudnik-Schöneborn S, Pope K, Howell KB, McLean CA, Kornberg AJ, Joseph J, Lockhart PJ, Zerres K, Ryan MM, Nelson SF, Koehler CM, Jen JC. Loss of function of SLC25A46 causes lethal congenital pontocerebellar hypoplasia. Brain. 2016;139(11):2877–90.

    Article  PubMed  PubMed Central  Google Scholar 

  185. Wang J, Wechsler-Reya RJ. The role of stem cells and progenitors in the genesis of medulloblastoma. Exp Neurol. 2014;260(1090–2430 (Electronic)):69–73.

    Article  CAS  PubMed  Google Scholar 

  186. Wang ZY, Miki T, Lee KY, Yokoyama T, Kusaka T, Sumitani K, Warita K, Matsumoto Y, Yakura T, Hosomi N, Ameno K, Bedi KS, Takeuchi Y. Short-term exposure to ethanol causes a differential response between nerve growth factor and brain-derived neurotrophic factor ligand/receptor Systems in the Mouse Cerebellum. Neuroscience. 2010;165(2):485–91.

    Article  CAS  PubMed  Google Scholar 

  187. Wang C, Pan YH, Wang Y, Blatt G, Yuan XB. Segregated expressions of autism risk genes Cdh11 and Cdh9 in autism-relevant regions of developing cerebellum. Mol Brain. 2019;12(1):40.

    Article  PubMed  PubMed Central  Google Scholar 

  188. Xifro X, Rodriguez-Alvarez J. Delineating the factors and cellular mechanisms involved in the survival of cerebellar granule neurons. Cerebellum. 2015;14(3):354–9.

    Article  PubMed  Google Scholar 

  189. Xiong P, Zeng Y, Zhu Z, Tan D, Xu F, Lu J, Wan J, Ma M. Reduced NGF serum levels and abnormal P300 event-related potential in first episode schizophrenia. Schizophr Res. 2010;119(1–3):34–9.

    Article  PubMed  Google Scholar 

  190. Xiong P, Zeng Y, Wan J, Xiaohan DH, Tan D, Lu J, Xu F, Li HY, Zhu Z, Ma M. The role of NGF and IL-2 serum level in assisting the diagnosis in first episode schizophrenia. Psychiatry Res. 2011;189(1):72–6.

    Article  CAS  PubMed  Google Scholar 

  191. Xiong P, Zeng Y, Wu Q, Han Huang DX, Zainal H, Xu X, Wan J, Xu F, Lu J. Combining serum protein concentrations to diagnose schizophrenia: a preliminary exploration. J Clin Psychiatry. 2014;75(8):e794–801.

    Article  CAS  PubMed  Google Scholar 

  192. Xu M, Sajdel-Sulkowska EM, Iwasaki T, Koibuchi N. Aberrant cerebellar neurotrophin-3 expression induced by lipopolysaccharide exposure during brain development. Cerebellum. 2013;12(3):316–8.

    Article  CAS  PubMed  Google Scholar 

  193. Yang B, Ren Q, Zhang JC, Chen QX, Hashimoto K. Altered expression of BDNF, BDNF pro-peptide and their precursor proBDNF in brain and liver tissues from psychiatric disorders: rethinking the brain-liver axis. Transl Psychiatry. 2017;7(5):e1128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Zakharyan R, Atshemyan S, Gevorgyan A, Boyajyan A. Nerve growth factor and its receptor in schizophrenia. BBA Clin. 2014;1(2214–6474 (Electronic)):24–9.

    Article  PubMed  PubMed Central  Google Scholar 

  195. Zanin JP, Verpeut JL, Li Y, Shiflett MW, Wang SS. The p75NTR Influences Cerebellar Circuit Development and Adult Behavior via Regulation of Cell Cycle Duration of Granule Cell Progenitors. J Neurosci. 2019;39(46):9119–29.

    Article  PubMed  PubMed Central  Google Scholar 

  196. Zeni CP, Tramontina S, Aguiar BW, Salatino-Oliveira A, Pheula GF, Sharma A, Stertz L, Moreira Maia CR, Hutz M, Kapczinski FP, Rohde LA. BDNF Val66Met polymorphism and peripheral protein levels in pediatric bipolar disorder and attention-deficit/hyperactivity disorder. Acta Psychiatr Scand. 2016;134(3):268–74.

    Article  CAS  PubMed  Google Scholar 

  197. Zhu J, Wang HT, Chen YR, Yan LY, Han YY, Liu LY, Cao Y, Liu ZZ, Xu HA. The Joubert syndrome gene arl13b is critical for early cerebellar development in zebrafish. Neurosci Bull. 2020;36(9):1023–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Zocher M, Czub S, Schulte-Monting J, de La Torre JC, Sauder C. Alterations in neurotrophin and neurotrophin receptor gene expression patterns in the rat central nervous system following perinatal Borna disease virus infection. J Neurovirol. 2000;6(6):462–77.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Pharmacology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Leila Pirmoradi

  2. Section of Neurosurgery, Department of Surgery, Faculty of Health Science, College of Medicine, University of Manitoba, Winnipeg, Canada

    Shahla Shojaei

Authors
  1. Leila Pirmoradi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shahla Shojaei
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shahla Shojaei .

Editor information

Editors and Affiliations

  1. Department of Human Anatomy and Cell Science The Children’s Hospital Research Institute of Manitoba (CHRIM) Max Rady College of Medicine Rady Faculty of Health Science, University of Manitoba, Winnipeg, MB, Canada

    Hassan Marzban

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Pirmoradi, L., Shojaei, S. (2023). Developmental Disorders of the Cerebellum and Neurotrophic Factors. In: Marzban, H. (eds) Development of the Cerebellum from Molecular Aspects to Diseases. Contemporary Clinical Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-031-23104-9_10

Download citation

Publish with us

Policies and ethics

Search

Navigation