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Neurotrophins and Cell Death

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Neurodevelopmental Pediatrics

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Abstract

Early in development, the nervous system overproduces neurons and synapses. Throughout development, this initial surplus of cells is reduced and the connections between them refined via tightly controlled cell death. Cell death is regulated by a family of secreted proteins known as the neurotrophins. The four members of this family, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4), have unique expression patterns and act through their receptors on distinct neuronal populations at different stages throughout development and in adulthood. In addition to controlling the balance between neuronal survival and cell death, neurotrophins regulate neuronal differentiation, connectivity and function, making them essential for proper nervous system development. Dysregulation of neurotrophins or their receptors at critical stages during development results in neurodevelopmental disorders that arise from perturbations in neuronal survival, proliferation, differentiation, synaptic function, connectivity, and plasticity.

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Abbreviations

Akt:

Protein kinase B

APAF-1:

Apoptotic protease activating factor 1

ASD:

Autism spectrum disorder

BDNF:

Brain-derived neurotrophic factor

BMP:

Bone morphogenic protein

Cl−:

Chloride

CNS:

Central nervous system

CREB:

cAMP response element-binding protein

Cyt c:

Cytochrome c/ cytochrome complex

DLPFC:

Dorsolateral prefrontal cortex

DNA:

Deoxyribonucleic acid

DRG:

Dorsal root ganglia

E:

Embryonic day

Elk-1:

E26 transformation-specific-like protein 1

E-LTP:

Early-phase long-term potentiation

ENS:

Enteric nervous system

EPS-8:

Epidermal growth factor receptor kinase substrate 8

ERK:

Extracellular signal-regulated kinase

FADD:

Fas-associated protein with death domain

FRS2:

Fibroblast growth factor substrate 2

GABA:

ɣ-aminobutyric acid

GDI:

Guanine-nucleotide dissociation inhibitor

GDNF:

Glial cell line-derived neurotrophic factor

GRB2:

Growth factor receptor-bound protein 2

IPSC:

Inhibitory postsynaptic potential

JNK:

c-Jun N-terminal kinase

KCC2:

Potassium chloride cotransporter 2

LGN:

Lateral geniculate nucleus

LTD:

Long-term depression

LTP:

Long-term potentiation

L-LTP:

Late-phase long-term potentiation

MAG:

Myelin-associated glycoprotein

MAP:

Mitogen-activated protein kinase

MBP:

Myelin basic protein

mEPSC:

Mini excitatory postsynaptic current

mRNA:

Messenger ribonucleic acid

MS:

Multiple sclerosis

mTOR:

Mammalian target of rapamycin

NKCC1:

Na-K-Cl cotransporter

NMDA:

N-methyl-D-aspartate receptor

NGF:

Nerve growth factor

NF-κB:

Nuclear factor-κB

Nogo-R:

Nogo-66 receptor

NR2B:

N-methyl D-aspartate receptor subtype 2B

NRAGE:

Neurotrophin receptor-interacting melanoma antigen gene homolog

NRIF:

Neurotrophin receptor interacting factor

NT-3:

Neurotrophin 3

NT-4:

Neurotrophin 4

OMgp:

Oligodendrocyte-myelin glycoprotein

P:

Postnatal day

p75NTR:

Pan-neurotrophin receptor

PCD:

Programmed cell death

PI3K:

Phosphoinositide-3′-kinase

PKC:

Protein kinase C

PLC-γ1:

Phospholipase C gamma-1

PNS:

Peripheral nervous system

PSD95:

Postsynaptic density protein 95

SC-1:

Schwann cell factor 1

SHC:

Src homology 2 domain containing

SNP:

Single-nucleotide polymorphisms

SorCS2:

Sortilin-related VPS10 domain containing receptor 2

SOS:

Son of sevenless

RhoA:

Ras homolog family member A

ROCK:

Rho-associated protein kinase

TGF-β:

Transforming growth factor-β

TLE:

Temporal lobe epilepsy

TRAF:

Tumor necrosis factor receptor-associated factor

Trk:

Tropomyosin-related kinase

References

  1. Maghsoudi N, Zakeri Z, Lockshin RA. Programmed cell death and apoptosis - where it came from and where it is going: from Elie Metchnikoff to the control of caspases. Exp Oncol. 2012;34(3):146–52.

    CAS  Google Scholar 

  2. Kuan CY, Roth KA, Flavell RA, Rakic P. Mechanisms of programmed cell death in the developing brain. Trends Neurosci. 2000;23(7):291–7.

    Article  CAS  Google Scholar 

  3. Yamaguchi Y, Miura M. Programmed cell death in neurodevelopment. Dev Cell. 2015;32(4):478–90.

    Article  CAS  Google Scholar 

  4. Shi Y. Caspase activation, inhibition, and reactivation: a mechanistic view. Protein Sci. 2004;13(8):1979–87.

    Article  CAS  Google Scholar 

  5. Nijhawan D, Honarpour N, Wang X. Apoptosis in neural development and disease. Annu Rev Neurosci. 2000;23:73–87.

    Article  CAS  Google Scholar 

  6. Cecconi F, Alvarez-Bolado G, Meyer BI, Roth KA, Gruss P. Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development. Cell. 1998;94(6):727–37.

    Article  CAS  Google Scholar 

  7. Kuan CY, Yang DD, Samanta Roy DR, Davis RJ, Rakic P, Flavell RA. The Jnk1 and Jnk2 protein kinases are required for regional specific apoptosis during early brain development. Neuron. 1999;22(4):667–76.

    Article  CAS  Google Scholar 

  8. Sabapathy K, Jochum W, Hochedlinger K, Chang L, Karin M, Wagner EF. Defective neural tube morphogenesis and altered apoptosis in the absence of both JNK1 and JNK2. Mech Dev. 1999;89(1–2):115–24.

    Article  CAS  Google Scholar 

  9. Hamburger V, Levi-Montalcini R. Proliferation, differentiation and degeneration in the spinal ganglia of the chick embryo under normal and experimental conditions. J Exp Zool. 1949;111(3):457–501.

    Article  CAS  Google Scholar 

  10. Levi-Montalcini R. The nerve growth factor 35 years later. Science. 1987;237(4819):1154–62.

    Article  CAS  Google Scholar 

  11. Huang EJ, Reichardt L. Neurotrophins: Roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677–736.

    Article  CAS  Google Scholar 

  12. Levi-Montalcini R, Angeletti PU. Nerve growth factor. Physiol Rev. 1968;48(3):534–69.

    Article  CAS  Google Scholar 

  13. Davies AM. The neurotrophic hypothesis: where does it stand? Philos Trans R Soc B Biol Sci. 1996;351(1338):389–94.

    Article  CAS  Google Scholar 

  14. Davies AM. Regulation of neuronal survival and death by extracellular signals during development. EMBO J. 2003;22(11):2537–45.

    Article  CAS  Google Scholar 

  15. Cowan WM. Viktor Hamburger and Rita Levi-Montalcini: the path to the discovery of nerve growth factor. Annu Rev Neurosci. 2001;24(1):551–600.

    Article  CAS  Google Scholar 

  16. Barde YA, Edgar D, Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO J. 1982;1(5):549–53.

    Article  CAS  Google Scholar 

  17. Hohn A, Leibrock J, Bailey K, Barde Y-A. Identification and characterization of a novel member of the nerve growth factor /brain-derived neurotrophic factor family. Nature. 1990;344(March):339–41.

    Article  CAS  Google Scholar 

  18. Maisonpierre P, Belluscio L, Squinto S, Ip N, Furth M, Lindsay R, et al. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science. 1990;247(4949):1446–51.

    Article  CAS  Google Scholar 

  19. Ip NY, Ibanez CF, Nye SH, McClain J, Jones PF, Gies DR, et al. Mammalian neurotrophin-4: structure, chromosomal localization, tissue distribution, and receptor specificity. Proc Natl Acad Sci U S A. 1992;89(7):3060–4.

    Article  CAS  Google Scholar 

  20. Hallböök F, Ibáñez CF, Persson H. Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in xenopus ovary. Neuron. 1991;6(5):845–58.

    Article  Google Scholar 

  21. Berkemeier LR, Winslow JW, Kaplan DR, Nikolics K, Goeddel DV, Rosenthal A. Neurotrophin-5: a novel neurotrophic factor that activates trk and trkB. Neuron. 1991;7(5):857–66.

    Article  CAS  Google Scholar 

  22. Deinhardt K, Chao MV. Trk Receptors. Trk Receptors Handb Exp Pharmacol. 2014;220:103–19.

    Article  CAS  Google Scholar 

  23. Eide FF, Vining ER, Eide BL, Zang K, Wang XY, Reichardt LF. Naturally occurring truncated trkB receptors have dominant inhibitory effects on brain-derived neurotrophic factor signaling. J Neurosci. 1996;16(10):3123–9.

    Article  CAS  Google Scholar 

  24. Fulgenzi G, Tomassoni-Ardori F, Babini L, Becker J, Barrick C, Puverel S, et al. BDNF modulates heart contraction force and long-term homeostasis through truncated TrkB.T1 receptor activation. J Cell Biol. 2015;210(6):1003–12.

    Article  CAS  Google Scholar 

  25. Gentry JJ, Barker PA, Carter BD. The p75 neurotrophin receptor: multiple interactors and numerous functions. Prog Brain Res. 2004;146:25–39.

    Article  CAS  Google Scholar 

  26. Chao MV. Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci. 2003;4(4):299–309.

    Article  CAS  Google Scholar 

  27. Mahadeo D, Kaplan L, Chao MV, Hempstead BL. High affinity nerve growth factor binding displays a faster rate of association than p140trk binding. J Biol Chem. 1994;269(9):6884–91.

    Article  CAS  Google Scholar 

  28. Schwab ME. Nogo and axon regeneration. Curr Opin Neurobiol. 2004;14(1):118–24.

    Article  CAS  Google Scholar 

  29. Nykjaer A, Lee R, Teng KK, Jansen P, Madsen P, Nielsen MS, et al. Sortilin is essential for proNGF- induced neuronal cell death. Nature. 2004;427(6977):843–8.

    Article  CAS  Google Scholar 

  30. Lu B, Pang PT, Woo NH. The yin and yang of neurotrophin action. Nat Rev Neurosci. 2005;6(8):603–14.

    Article  CAS  Google Scholar 

  31. Kraemer BR, Yoon SO, Carter BD. The biological functions and signaling mechanisms of the p75 Neurotrophin receptor. Handb Exp Pharmacol. 2014;220:121–64.

    Article  CAS  Google Scholar 

  32. Kaplan DR, Miller FD. Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol. 2000;10(3):381–91.

    Article  CAS  Google Scholar 

  33. Fahnestock M, Shekari A. ProNGF and neurodegeneration in Alzheimer’s disease. Front Neurosci. 2019;13:129.

    Article  Google Scholar 

  34. Teng HK, Teng KK, Lee R, Wright S, Tevar S, Almeida RD, et al. ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75 NTR and sortilin. J Neurosci. 2005;25(22):5455–63.

    Article  CAS  Google Scholar 

  35. Koshimizu H, Kiyosue K, Hara T, Hazama S, Suzuki S, Uegaki K, et al. Multiple functions of precursor BDNF to CNS neurons: negative regulation of neurite growth, spine formation and cell survival. Mol Brain. 2009;2:27.

    Article  Google Scholar 

  36. Fahnestock M, Michalski B, Xu B, Coughlin MD. The precursor pro-nerve growth factor is the predominant form of nerve growth factor in brain and is increased in Alzheimer’s disease. Mol Cell Neurosci. 2001;18(2):210–20.

    Article  CAS  Google Scholar 

  37. Masoudi R, Ioannou MS, Coughlin MD, Pagadala P, Neet KE, Clewes O, et al. Biological activity of nerve growth factor precursor is dependent upon relative levels of its receptors. J Biol Chem. 2009;284(27):18424–33.

    Article  CAS  Google Scholar 

  38. Bothwell M. NGF, BDNF, NT3, and NT4. Handb Exp Pharmacol. 2014;220:3–15.

    Article  CAS  Google Scholar 

  39. Howe CL, Mobley WC. Long-distance retrograde neurotrophic signaling. Curr Opin Neurobiol. 2005;15(1):40–8.

    Article  CAS  Google Scholar 

  40. De Nadai T, Marchetti L, Di Rienzo C, Calvello M, Signore G, Di Matteo P, et al. Precursor and mature NGF live tracking: one versus many at a time in the axons. Sci Rep. 2016;6:20272.

    Article  Google Scholar 

  41. Shekari A, Fahnestock M. Retrograde axonal transport of BDNF and proNGF diminishes with age in basal forebrain cholinergic neurons. Neurobiol Aging. 2019;84:131–40.

    Article  CAS  Google Scholar 

  42. Ioannou MS, Fahnestock M. ProNGF, but not NGF, switches from neurotrophic to apoptotic activity in response to reductions in TrKA receptor levels. Int J Mol Sci. 2017;18(3):599.

    Article  Google Scholar 

  43. Holtzman DM, Kilbridge J, Li Y, Cunningham ET, Lenn NJ, Clary DO, et al. TrkA expression in the CNS: evidence for the existence of several novel NGF-responsive CNS neurons. J Neurosci. 1995;15(2):1567–76.

    Article  CAS  Google Scholar 

  44. Hartikka J, Hefti F. Development of septal cholinergic neurons in culture: plating density and glial cells modulate effects of NGF on survival, fiber growth, and expression of transmitter-specific enzymes. J Neurosci. 1988;8(8):2967–85.

    Article  CAS  Google Scholar 

  45. Bierl MA, Jones EE, Crutcher KA, Isaacson LG. “Mature” nerve growth factor is a minor species in most peripheral tissues. Neurosci Lett. 2005;380(1–2):133–7.

    Article  CAS  Google Scholar 

  46. Maisonpierre PC, Belluscio L, Friedman B, Alderson RF, Wiegand SJ, Furth ME, et al. NT-3, BDNF, and NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expression. Neuron. 1990;5(4):501–9.

    Article  CAS  Google Scholar 

  47. Thoenen H, Barde YA. Physiology of nerve growth factor. Physiol Rev. 1980;60(4):1284–335.

    Article  CAS  Google Scholar 

  48. Aloe L, Rocco M, Balzamino B, Micera A. Nerve growth factor: a focus on neuroscience and therapy. Curr Neuropharmacol. 2015;13(3):294–303.

    Article  CAS  Google Scholar 

  49. Grimes ML, Zhou J, Beattie EC, Yuen EC, Hall DE, Valletta JS, et al. Endocytosis of activated TrkA: evidence that nerve growth factor induces formation of signaling endosomes. J Neurosci. 1996;16(24):7950–64.

    Article  CAS  Google Scholar 

  50. Sieber-Blum M. Role of the neurotrophic factors BDNF and NGF in the commitment of pluripotent neural crest cells. Neuron. 1991;6(6):949–55.

    Google Scholar 

  51. Jones KR, Fariñas I, Backus C, Reichardt LF. Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development. Cell. 1994;76(6):989–99.

    Article  CAS  Google Scholar 

  52. Ernfors P, Lee K, Jaenisch R. Mice lacking brain-derived neurotrophic factor develop with sensory deficits. Nature. 1994;368(March):147–50.

    Article  CAS  Google Scholar 

  53. Ernfors P, Van De Water T, Loring J, Jaenisch R. Complementary roles of BDNF and NT-3 in vestibular and auditory development. Neuron. 1995;14(6):1153–64.

    Article  Google Scholar 

  54. Conover JC, Erickson JT, Katz DM, Bianchi LM, Poueymirou WT, McClain J, et al. Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4. Nature. 1995;375(6528):235–8.

    Article  CAS  Google Scholar 

  55. Acheson A, Conover JC, Fandl JP, DeChiara TM, Russell M, Thadani A, et al. A BDNF autocrine loop in adult sensory neurons prevents cell death. Nature. 1995;374(6521):450–3.

    Article  CAS  Google Scholar 

  56. Liu X, Jaenisch R. Severe peripheral sensory neuron loss and modest motor neuron reduction in mice with combined deficiency of brain-derived neurotrophic factor, neurotrophin 3 and neurotrophin 4/5. Dev Dyn. 2000;218(1):94–101.

    Article  CAS  Google Scholar 

  57. Cohen-Cory S, Kidane AH, Shirkey NJ, Marshak S. Brain-derived neurotrophic factor and the development of structural neuronal connectivity. Dev Neurobiol. 2010 Apr;70(5):271–88.

    Google Scholar 

  58. Borghesani PR, Peyrin JM, Klein R, Rubin J, Carter AR, Schwartz PM, et al. BDNF stimulates migration of cerebellar granule cells. Development. 2002;129:1435–42.

    Article  CAS  Google Scholar 

  59. Liu X, Somel M, Tang L, Yan Z, Jiang X, Guo S, et al. Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques. Genome Res. 2012;22(4):611–22.

    Article  CAS  Google Scholar 

  60. Webster MJ, Weickert CS, Herman MM, Kleinman JE. BDNF mRNA expression during postnatal development, maturation and aging of the human prefrontal cortex. Dev Brain Res. 2002;139(2):139–50.

    Article  CAS  Google Scholar 

  61. Xu B, Zang K, Ruff NL, Zhang YA, McConnell SK, Stryker MP, et al. Cortical degeneration in the absence of neurotrophin signaling: dendritic retraction and neuronal loss after removal of the receptor TrkB. Neuron. 2000;26(1):233–45.

    Article  CAS  Google Scholar 

  62. Cohen-Cory S, Fraser SE. BDNF in the development of the visual system of Xenopus. Neuron. 1994;12(4):747–61.

    Article  CAS  Google Scholar 

  63. Shatz CJ, Stryker MP. Ocular dominance in layer IV of the cat’s visual cortex and the effects of monocular deprivation. J Physiol. 1978;281(1):267–83.

    Article  CAS  Google Scholar 

  64. Hubel DH, Wiesel TN, LeVay S. Plasticity of ocular dominance columns in monkey striate cortex. Philos Trans R Soc B Biol Sci. 1977;278(961):377–409.

    CAS  Google Scholar 

  65. Domenici L, Berardi N, Carmignoto G, Vantini G, Maffei L. Nerve growth factor prevents the amblyopic effects of monocular deprivation. Proc Natl Acad Sci U S A. 1991;88(19):8811–5.

    Article  CAS  Google Scholar 

  66. McAllister AK, Katz LC, Lo DC. Opposing roles for endogenous BDNF and NT-3 in regulating cortical dendritic growth. Neuron. 1997;18(5):767–78.

    Article  CAS  Google Scholar 

  67. Cabelli RJ, Shelton DL, Segal RA, Shatz CJ. Blockade of endogenous ligands of TrkB inhibits formation of ocular dominance columns. Neuron. 1997;19(1):63–76.

    Article  CAS  Google Scholar 

  68. Cellerino A, Maffei L, Domenici L. The distribution of brain-derived neurotrophic factor and its receptor trkB in parvlbumin-containing neurons of the rat visual cortex. Eur J Neurosci. 1996;8(6):1190–7.

    Article  CAS  Google Scholar 

  69. Porcher C, Medina I, Gaiarsa JL. Mechanism of BDNF modulation in GABAergic synaptic transmission in healthy and disease brains. Front Cell Neurosci. 2018;12(August):1–9.

    Google Scholar 

  70. Fiorentino H, Kuczewski N, Diabira D, Ferrand N, Pangalos MN, Porcher C, et al. GABAB receptor activation triggers BDNF release and promotes the maturation of GABAergic synapses. J Neurosci. 2009;29(37):11650–61.

    Article  CAS  Google Scholar 

  71. Ben-Ari Y, Gaiarsa J, Tyzio R, Khazipov R. GABA : a pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiol Rev. 2007;87:1215–84.

    Article  CAS  Google Scholar 

  72. Lu B, Nagappan G, Lu Y. BDNF and synaptic plasticity, cognitive function, and dysfunction. Handb Exp Pharmacol. 2014;220:223–50.

    Article  CAS  Google Scholar 

  73. Kandel ER. The molecular biology of memory storage: a dialogue between genes and synapses. Science. 2001;294(5544):1030–8.

    Article  CAS  Google Scholar 

  74. Korte M, Carroll P, Wolf E, Brem G, Thoenen H, Bonhoeffer T. Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Proc Natl Acad Sci U S A. 1995;92(19):8856–60.

    Article  CAS  Google Scholar 

  75. Minichiello L, Korte M, Wolfer D, Kühn R, Unsicker K, Cestari V, et al. Essential role for TrkB receptors in hippocampus-mediated learning. Neuron. 1999;24(2):401–14.

    Article  CAS  Google Scholar 

  76. Yang J, Harte-Hargrove LC, Siao C, Marinic T, Clarke R, Ma Q, et al. proBDNF negatively regulates neuronal remodeling, synaptic transmission, and synaptic plasticity in hippocampus. Cell Rep. 2014;7(3):796–806.

    Article  CAS  Google Scholar 

  77. Proenca CC, Song M, Lee FS. Differential effects of BDNF and neurotrophin 4 (NT4) on endocytic sorting of TrkB receptors. J Neurochem. 2017;138(3):397–406.

    Article  Google Scholar 

  78. Lodovichi C, Berardi N, Pizzorusso T, Maffei L. Effects of neurotrophins on cortical plasticity: same or different? J Neurosci. 2000;20(6):2155–65.

    Article  CAS  Google Scholar 

  79. Minichiello L, Casagranda F, Tatche RS, Stucky CL, Postigo A, Lewin GR, et al. Point mutation in trkB causes loss of NT4-dependent neurons without major effects on diverse BDNF responses. Neuron. 1998;21(2):335–45.

    Article  CAS  Google Scholar 

  80. Chalazonitis A, Pham TD, Rothman TP, DiStefano PS, Bothwell M, Blair-Flynn J, et al. Neurotrophin-3 is required for the survival–differentiation of subsets of developing enteric neurons. J Neurosci. 2001;21(15):5620–36.

    Article  CAS  Google Scholar 

  81. Chalazonitis A. Neurotrophin-3 in the development of the enteric nervous system. Prog Brain Res. 2004;146:243–63.

    Article  CAS  Google Scholar 

  82. Stewart AL, Anderson RB, Kobayashi K, Young HM. Effects of NGF, NT-3 and GDNF family members on neurite outgrowth and migration from pelvic ganglia from embryonic and newborn mice. BMC Dev Biol. 2008;8(1):1–15.

    Article  Google Scholar 

  83. Nagy N, Goldstein AM. Enteric nervous system development: a crest cell’s journey from neural tube to colon. Semin Cell Dev Biol. 2017;66:94–106.

    Article  Google Scholar 

  84. Kuruvilla R, Zweifel LS, Glebova NO, Lonze BE, Valdez G, Ye H, et al. A neurotrophin signaling cascade coordinates sympathetic neuron development through differential control of TrkA trafficking and retrograde signaling. Cell. 2004;118(2):243–55.

    Article  CAS  Google Scholar 

  85. Coelho RP, Yuelling LM, Fuss B, Sato-Bigbee C. Neurotrophin-3 targets the translational initiation machinery in oligodendrocytes. Glia. 2009;57(16):1754–64.

    Article  Google Scholar 

  86. Glebova NO, Ginty DD. Growth and survival signals controlling sympathetic nervous system development. Annu Rev Neurosci. 2005;28(1):191–222.

    Article  CAS  Google Scholar 

  87. Francis N, Farinas I, Brennan C, Rivas-Plata K, Backus C, Reichardt L, et al. NT-3, like NGF, is required for survival of sympathetic neurons, but not their precursors. Dev Biol. 1999;210(2):411–27.

    Article  CAS  Google Scholar 

  88. Krimm RF, Davis BM, Albers KM. Cutaneous overexpression of neurotrophin-3 (NT3) selectively restores sensory innervation in NT3 gene knockout mice. J Neurobiol. 2000;43(1):40–9.

    Article  CAS  Google Scholar 

  89. Kumar A, Pareek V, Faiq MA, Ghosh SK, Kumari C. Adult neurogenesis in humans: a review of basic concepts, history, current research, and clinical implications. Innov Clin Neurosci. 2019;16(5–6):30–7.

    CAS  Google Scholar 

  90. Yau S, Li A, So K-F. Involvement of adult hippocampal neurogenesis in learning and forgetting. Neural Plast. 2015;2015:1–13.

    Article  Google Scholar 

  91. Numakawa T, Odaka H, Adachi N. Actions of brain-derived neurotrophic factor and glucocorticoid stress in neurogenesis. Int J Mol Sci. 2017;18(11):2312.

    Article  Google Scholar 

  92. Troca-Marín JA, Alves-Sampaio A, Montesinos ML. Deregulated mTOR-mediated translation in intellectual disability. Prog Neurobiol. 2012;96(2):268–82.

    Article  Google Scholar 

  93. Nicolini C, Ahn Y, Michalski B, Rho JM, Fahnestock M. Decreased mTOR signaling pathway in human idiopathic autism and in rats exposed to valproic acid. Acta Neuropathol Commun. 2015;3(3):1–13.

    Google Scholar 

  94. Nicolini C, Fahnestock M. The valproic acid-induced rodent model of autism. Exp Neurol. 2018;299:217–27.

    Article  CAS  Google Scholar 

  95. Sandin S, Lichtenstein P, Kuja-Halkola R, Larsson H, Hultman CM, Reichenberg A. The familial risk of autism. JAMA. 2014;311(17):1770–7.

    Article  CAS  Google Scholar 

  96. Kelleher RJ, Bear MF. The autistic neuron: troubled translation? Cell. 2008;135(3):401–6.

    Article  CAS  Google Scholar 

  97. Morimoto K, Fahnestock M, Racine RJ. Kindling and status epilepticus models of epilepsy: rewiring the brain. Prog Neurobiol. 2004;73(1):1–60.

    Article  CAS  Google Scholar 

  98. Adams B, Sazgar M, Osehobo P, Van der Zee CEEM, Diamond J, Fahnestock M, et al. Nerve growth factor accelerates seizure development, enhances mossy fiber sprouting, and attenuates seizure-induced decreases in neuronal density in the kindling model of epilepsy. J Neurosci. 1997;17(14):5288–96.

    Article  CAS  Google Scholar 

  99. Ben-Ari Y, Holmes GL. The multiple facets of γ-aminobutyric acid dysfunction in epilepsy. Curr Opin Neurol. 2005;18(2):141–5.

    Article  CAS  Google Scholar 

  100. Boschen KE, Klintsova AY. Neurotrophins in the brain: interaction with alcohol exposure during development. Vitam Horm. 2017;4(104):197–242.

    Article  Google Scholar 

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Authors and Affiliations

  1. McMaster University, Hamilton, ON, Canada

    Arman Shekari, Crystal Mahadeo, Nisha Sanwalka & Margaret Fahnestock

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  1. Arman Shekari
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  2. Crystal Mahadeo
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  4. Margaret Fahnestock
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Correspondence to Margaret Fahnestock .

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Editors and Affiliations

  1. Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia

    David D. Eisenstat

  2. Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada

    Dan Goldowitz

  3. Department of Pediatrics and School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada

    Tim F. Oberlander

  4. Department of Pediatrics, University of Alberta, Edmonton, AB, Canada

    Jerome Y. Yager

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Shekari, A., Mahadeo, C., Sanwalka, N., Fahnestock, M. (2023). Neurotrophins and Cell Death. In: Eisenstat, D.D., Goldowitz, D., Oberlander, T.F., Yager, J.Y. (eds) Neurodevelopmental Pediatrics. Springer, Cham. https://doi.org/10.1007/978-3-031-20792-1_4

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