Metabolic Brain Disease

, Volume 33, Issue 3, pp 693–704 | Cite as

Methylphenidate disrupts cytoskeletal homeostasis and reduces membrane-associated lipid content in juvenile rat hippocampus

  • Felipe Schmitz
  • Paula Pierozan
  • Helena Biasibetti-Brendler
  • Fernanda Silva Ferreira
  • Fernanda dos Santos Petry
  • Vera Maria Treis Trindade
  • Regina Pessoa-Pureur
  • Angela T. S. Wyse
Original Article


Although methylphenidate (MPH) is ubiquitously prescribed to children and adolescents, the consequences of chronic utilization of this psychostimulant are poorly understood. In this study, we investigated the effects of MPH on cytoskeletal homeostasis and lipid content in rat hippocampus. Wistar rats received intraperitoneal injections of MPH (2.0 mg/kg) or saline solution (controls), once a day, from the 15th to the 44th day of age. Results showed that MPH provoked hypophosphorylation of glial fibrillary acidic protein (GFAP) and reduced its immunocontent. Middle and high molecular weight neurofilament subunits (NF-M, NF-H) were hypophosphorylated by MPH on KSP repeat tail domains, while NFL, NFM and NFH immunocontents were not altered. MPH increased protein phosphatase 1 (PP1) and 2A (PP2A) immunocontents. MPH also decreased the total content of ganglioside and phospholipid, as well as the main brain gangliosides (GM1, GD1a, and GD1b) and the major brain phospholipids (sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine). Total cholesterol content was also reduced in the hippocampi of juvenile rats treated with MPH. These results provide evidence that disruptions of cytoskeletal and lipid homeostasis in hippocampus of juvenile rats are triggers by chronic MPH treatment and present a new basis for understanding the effects and consequences associated with chronic use of this psychostimulant during the development of the central nervous system.


Methylphenidate Cytoskeleton Intermediate filaments Cholesterol Gangliosides Phospholipids 



Attention deficit hyperactivity disorder


Central nervous system


Glial fibrillary acidic protein


Intermediate filaments








High molecular weight neurofilament subunit


Light molecular weight neurofilament subunit


Middle molecular weight neurofilament subunit


Protein phosphatase 1


Protein phosphatase 2A





This work was supported in part by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq–Brazil).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest with the contents of this article.


  1. Adibhatla RM, Hatcher JF (2007) Role of lipids in brain injury and diseases. Future Lipidol 2(4):403–422. CrossRefPubMedPubMedCentralGoogle Scholar
  2. Akay AP, Kaya GÇ, Emiroglu NI, Aydin A, Monkul ES, Tasçi C et al (2006) Effects of long-term methylphenidate treatment: a pilot follow-up clinical and SPECT study. Prog Neuropsychopharmacol Biol Psychiatry 30:1219–1224CrossRefPubMedGoogle Scholar
  3. Andersen SL (2005) Stimulants and the developing brain. Trends Pharmacol Sci 26(5):237–243. CrossRefPubMedGoogle Scholar
  4. Andersen SL, Napierata L, Brenhouse HC, Sonntag KC (2008) Juvenile methyphenidate modulates reward-related behaviours and cerebral blood flow by decreasing cortical D3 receptors. Eur J Neurosci 27(11):2962–2972. CrossRefPubMedGoogle Scholar
  5. Andreazza AC, Frey BN, Valvassori SS, Zanotto C, Gomes KM, Comim CM, Cassini C, Stertz L, Ribeiro LC, Quevedo J, Kapczinski F, Berk M, Gonçalves CA (2007) DNA damage in rats after treatment with methylphenidate. Prog Neuro-Psychopharmacol Biol Psychiatry 31(6):1282–1288. CrossRefGoogle Scholar
  6. Banerjee PS, Aston J, Khundakar AA, Zetterström T (2009) Differential regulation of psychostimulant-induced gene expression of brain derived neurotrophic factor and the immediate-early gene Arc in the juvenile and adult brain. Eur J Neurosci 29(3):465–476. CrossRefPubMedGoogle Scholar
  7. Bartlett GR (1959) Phosphorus assay in column chromatography. J Biol Chem 234(3):466–468PubMedGoogle Scholar
  8. Brownlees J, Yates A, Bajaj NP, Davis D, Anderton BH, Leigh PN, Shaw CE, Miller CC (2000) Phosphorylation of neurofilament heavy chain side-arms by stress activated protein kinase-1b/Jun N-terminal kinase-3. J Cell Sci 113:401–407PubMedGoogle Scholar
  9. Chase T, Carrey N, Soo E, Wilkinson M (2007) Methylphenidate regulates activity cytoskeletal associated but not brain-derived neurotrophic factor gene expression in the developing rat striatum. Neuroscience 144(3):969–984. CrossRefPubMedGoogle Scholar
  10. Cornelius F, Habeck M, Kanai R, Toyoshima C, Karlish SJD (2015) General and specific lipid–protein interactions in Na, K-ATPase. Biochim Biophys Acta 1848(9):1729–1743. CrossRefPubMedGoogle Scholar
  11. Cyr M, Beaulieu JM, Laakso A, Sotnikova TD, Yao WD, Bohn LM, Gainetdinov RR, Caron MG (2003) Sustained elevation of extracellular dopamine causes motor dysfunction and selective degeneration of striatal GABAergic neurons. Proc Natl Acad Sci U S A 100(19):11035–11040. CrossRefPubMedPubMedCentralGoogle Scholar
  12. Dafny N, Yang PB (2006) The role of age, genotype, sex, and route of acute and chronic administration of methylphenidate: a review of its locomotor effects. Brain Res Bull 68(6):393–405. CrossRefPubMedGoogle Scholar
  13. de Almeida LM, Funchal C, Pde Pelaez L, Pessutto FD, Loureiro SO, Vivian L, Wajner M, Pessoa-Pureur R (2003) Effect of propionic and methylmalonic acids on the in vitro phosphorylation of intermediate filaments from cerebral cortex of rats during development. Metab Brain Dis 18(3):207–219. CrossRefPubMedGoogle Scholar
  14. de Mattos-Dutra A, Sampaio de Freitas M, Schröder N, Fogaça Lisboa CS, Pessoa-Pureur R, Wajner M (1997) In vitro phosphorylation of cytoskeletal proteins in the rat cerebral cortex is decreased by propionic acid. Exp Neurol 147(2):238–247. CrossRefPubMedGoogle Scholar
  15. du Bois TM, Deng C, Huang XF (2005) Membrane phospholipid composition, alterations in neurotransmitter systems and schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry 29(6):878–888. CrossRefGoogle Scholar
  16. Fagundes AO, Rezin GT, Zanette F, Grandi E, Assis LC, Dal-Pizzol F, Quevedo J, Streck EL (2007) Chronic administration of methylphenidate activates mitochondrial respiratory chain in brain of young rats. Int J Dev Neurosci 25(1):47–51. CrossRefPubMedGoogle Scholar
  17. Fagundes AO, Aguiar MR, Aguiar CS, Scaini G, Sachet MU, Bernhardt NM, Rezin GT, Valvassori SS, Quevedo J, Streck EL (2010a) Effect of acute and chronic adminis tration of methylphenidate on mitochondrial respiratory chain in the brain of young rats. Neurochem Res 35(11):1675–1680. CrossRefPubMedGoogle Scholar
  18. Fagundes AO, Scaini G, Santos PM, Sachet MU, Bernhardt NM, Rezin GT, Valvassori SS, Schuck PF, Quevedo J, Streck EL (2010b) Inhibition of mitochondrial respiratory chain in the brain of adult rats after acute and chronic administration of methylphenidate. Neurochem Res 35(3):405–411. CrossRefPubMedGoogle Scholar
  19. Farooqui AA, Ong WY, Horrocks LA (2004) Biochemical aspects of neurodegeneration in human brain: involvement of neural membrane phospholipids and phospholipases A2. Neurochem Res 29(11):1961–1977. CrossRefPubMedGoogle Scholar
  20. Ferriero DM (2001) Oxidant mechanisms in neonatal hypoxia-ischemia. Dev Neurosci 23(3):198–202. CrossRefPubMedGoogle Scholar
  21. Folch J, Lees M, Sloane-Stanley GH (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226(1):497–509PubMedGoogle Scholar
  22. Fragoso ALR, Trindade VMT (2015) Resorcinol-HCl method adaption for N-acetyl neuraminic acid measurement in an aqueous medium, oral and poster communication. In: XXVII SALÃO DE INICIAÇÃO CIENTÍFICA DA UFRGS, Porto Alegre, RS, BrazilGoogle Scholar
  23. Friede RL, Samorajski T (1970) Axon caliber related to neurofilaments and microtubules in sciatic nerve fibers of rats and mice. Anat Rec 167(4):379–387. CrossRefPubMedGoogle Scholar
  24. Funchal C, de Almeida LM, Loureiro SO, Vivian L, de Lima PP, Dall Bello FP et al (2003) In vitro phosphorylation of cytoskeletal proteins from cerebral cortex of rats. Brain Res Prot 11(2):111–118. CrossRefGoogle Scholar
  25. Funchal C, Zamoner A, dos Santos AQ, Loureiro SO, Wajner M, Pessoa-Pureur R (2005) Alpha-ketoisocaproic acid increases phosphorylation of intermediate filament proteins from rat cerebral cortex by mechanisms involving Ca2+ and cAMP. Neurochem Res 30(9):1139–1146. CrossRefPubMedGoogle Scholar
  26. Gerasimov MR, Franceschi M, Volkow ND, Gifford A, Gatley SJ, Marsteller D et al (2000) Comparison between intraperitoneal and oral methylphenidate administration: a microdialysis and locomotor activity study. J Pharmacol Exp Ther 295:51–57PubMedGoogle Scholar
  27. Goldstein ME, Sternberger NH, Sternberger LA (1987) Phosphorylation protects neurofilaments against proteolysis. J Neuroimmunol 14(2):149–160. CrossRefPubMedGoogle Scholar
  28. Gonçalves J, Baptista S, Silva AP (2014) Psychostimulants and brain dysfunction: a review of the relevant neurotoxic effects. Neuropharmacology 87:135–149. CrossRefPubMedGoogle Scholar
  29. Gronier B, Aston J, Liauzun C, Zetterström T (2010) Age-dependent effects of methylphenidate in the prefrontal cortex: evidence from electrophysiological and arc gene expression measurements. J Psychopharmacol 24(12):1819–1827. CrossRefPubMedGoogle Scholar
  30. Guidato S, Bajaj NP, Miller CC (1996) Cellular phosphorylation of neurofilament heavy-chain by cyclin-dependent kinase-5 masks the epitope for monoclonal antibody N52. Neurosci Lett 217(2-3):157–160. CrossRefPubMedGoogle Scholar
  31. Hakansson K, Lindskog M, Pozzi L, Usiello A, Fisone G (2004) DARP-32 and modulation of cAMP signaling: involvement in motor control and levodopa induced dyskinesia. Parkinsonism Relat Disord 10(5):281–286. CrossRefPubMedGoogle Scholar
  32. Head BP, Patel HH, Insel PA (2014) Interaction of membrane/lipid rafts with the cytoskeleton: impact on signaling and function:membrane/lipid rafts, mediators of cytoskeletal arrangement and cell signaling. Biochim Biophys Acta 1838(2):532–545. CrossRefPubMedGoogle Scholar
  33. Heimfarth L, Loureiro SO, Reis KP, de Lima BO, Zamboni F, Lacerda S, Soska AK, Wild L, da Rocha JB, Pessoa-Pureur R (2012) Diphenyl ditelluride induces hypophosphorylation of intermediate filaments through modulation of DARPP-32-dependent pathways in cerebral cortex of young rats. Arch Toxicol 86(2):217–230. CrossRefPubMedGoogle Scholar
  34. Johnston LD, O’Malley PM, Bachman JG, Schulenberg JE (2011a) Monitoring the future national survey results on drug use, 1975–2010. Volume II: college students and adults ages 19–50. The University of Michigan, Bethesda, pp 1–312.
  35. Johnston LD, O’Malley PM, Bachman JG, Schulenberg JE (2011b) Monitoring the future national survey results on drug use, 1975–2010. Volume I: secondary school students. The University of Michigan, Bethesda, pp 1–734.
  36. Kabara JJ (1975) Brain cholesterol XVIII: EFFECt of methylphenidate (Ritalin) on [U-14C] glucose and [2-3H] acetate incorporation. Proc Soc Exp Biol Med 150(2):525–528. CrossRefPubMedGoogle Scholar
  37. Kronemberg G, Ende G, Alm B, Deuschle M, Heuser I, Colla M (2008) Increased NAA and reduced choline levels in the anterior cingulum following chronic methylphenidate. Eur Arch Psychiatry Clin Neurosci 258(7):446–450. CrossRefGoogle Scholar
  38. Kuczenski R, Segal DS (2001) Locomotor effects of acute and repeated threshold doses of amphetamine and methylphenidate: relative roles of dopamine and norepinephrine. J Pharmacol Exp Ther 296(3):876–883PubMedGoogle Scholar
  39. Kuczenski R, Segal DS (2002) Exposure of adolescent rats to oral methylphenidate: preferential effects on extracellular norepinephrine and absence of sensitization and cross-sensitization to methamphetamine. J Neurosci 22(16):7264–7271CrossRefPubMedGoogle Scholar
  40. Kudryashov IE, Onufriev MV, Kudryashova IV, Gulyaeva NV (2001) Periods of postnatal maturation of hippocampus: synaptic modifications and neuronal disconnection. Dev Brain Res 132(2):113–120. CrossRefGoogle Scholar
  41. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227(5259):680–685. CrossRefPubMedGoogle Scholar
  42. Lagace DC, Yee JK, Bolanos CA, Eisch AJ (2006) Juvenile administration of methylphenidate attenuates adult hippocampal neurogenesis. Biol Psychiatry 60(10):1121–1130. CrossRefPubMedGoogle Scholar
  43. Lake BD, Goodwin HJ (1976) Lipids. In: Smith I, Seakings JWT (eds) Chromatographic and Eletrophoretic techniques, Paper and thin layer chromatography, vol 1. William Heinemann Medical Books Ltd, London, pp 345–366Google Scholar
  44. Lee SB, Bagley JA, Lee HY, Jan LY, Jan YN (2011) Pathogenic polyglutamine proteins cause dendrite defects associated with specific actin cytoskeletal alterations in drosophila. Proc Natl Acad Sci U S A 108(40):16795–16800. CrossRefPubMedPubMedCentralGoogle Scholar
  45. Loureiro SO, Romão L, Alves T, Fonseca A, Heimfarth L, Neto VM, Wyse AT, Pessoa-Pureur R (2010) Homocysteine induces cytoskeletal remodeling and production of reactive oxygen species in cultured cortical astrocytes. Brain Res 1355:151–164. CrossRefPubMedGoogle Scholar
  46. Loureiro-Vieira S, Costa VM, de Lourdes Bastos M, Carvalho F, Capela JP (2017) Methylphenidate effects in the young brain: friend or foe? Int J Dev Neurosci 60:34–47. CrossRefPubMedGoogle Scholar
  47. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275PubMedGoogle Scholar
  48. Middeldorp J, Hol EM (2011) GFAP in health and disease. Prog Neurobiol 93(3):421–443. CrossRefPubMedGoogle Scholar
  49. Mocchetti I (2005) Exogenous gangliosides, neuronal plasticity and repair, and the neurotrophins. Cell Mol Life Sci 62(19-20):2283–2294. CrossRefPubMedGoogle Scholar
  50. Motaghinejad M, Motevalian M, Shabab B (2016) Effects of chronic treatment with methylphenidate on oxidative stress and inflammation in hippocampus of adult rats. Neurosci Lett 619:106–113. CrossRefPubMedGoogle Scholar
  51. Nakamura K, Handa S (1984) Coomassie brilliant blue staining of lipids on thin-layer plates. Anal Biochem 142(2):406–410. CrossRefPubMedGoogle Scholar
  52. Nores GA, Mitzumari RK, Kremer DM (1994) Chromatographic tank designed to obtain highly reproducible high-performance thin-layer chromatograms of gangliosides and neutral glycosphingolipids. J Chromatogr 686(1):155–157. CrossRefGoogle Scholar
  53. Nyakas C, Buwalda B, Luiten PG (1996) Hypoxia and brain development. Prog Neurobiol 49(1):1–51. CrossRefPubMedGoogle Scholar
  54. Ohvo-Rekilä H, Ramstedt B, Leppimäki P, Slotte JP (2002) Cholesterol interactions with phospholipids in membranes. Prog Lipid Res 41(1):66–97. CrossRefPubMedGoogle Scholar
  55. Omary MB, Ku NO, Tao GZ, Toivola DM, Liao J (2006) “Heads and tails” of intermediate filamento phosphorylation: multiple sites and functional insights. Trends Biochem Sci 31(7):383–394. CrossRefPubMedGoogle Scholar
  56. Pant HC (1988) Dephosphorylation of neurofilament proteins enhances their susceptibility to degradation by calpain. Biochem J 256(2):665–668. CrossRefPubMedPubMedCentralGoogle Scholar
  57. Pekny M, Pekna M (2004) Astrocyte intermediate filaments in CNS pathologies and regeneration. J Pathol 204(4):428–437. CrossRefPubMedGoogle Scholar
  58. Pfrieger FW (2003) Cholesterol homeostasis and function in neurons of the central nervous system. Cell Mol Life Sci 60:1158–1171CrossRefPubMedGoogle Scholar
  59. Phan NT, Fletcher JS, Ewing AG (2015) Lipid structural effects of oral administration of methylphenidate in drosophila brain by secondary ion mass spectrometry imaging. Anal Chem 87(8):4063–4071. CrossRefPubMedGoogle Scholar
  60. Pierozan P, Zamoner A, Soska AK, de Lima BO, Reis KP, Zamboni F, Wajner M, Pessoa-Pureur R (2012) Signaling mechanisms downstream of quinolinic acid targeting the cytoskeleton of rat striatal neurons and astrocytes. Exp Neurol 233(1):391–399. CrossRefPubMedGoogle Scholar
  61. Pierozan P, Gonçalves CF, Ferreira F, Pessoa-Pureur R (2014) Acute intrastriatal injection of quinolinic acid provokes long-lasting misregulation of the cytoskeleton in the striatum, cerebral cortex and hippocampus of young rats. Brain Res 1577:1–10. CrossRefPubMedGoogle Scholar
  62. Quansah E, Sgamma T, Jaddoa E, Zetterström TSC (2017a) Chronic methylphenidate regulates genes and proteins mediating neuroplasticity in the juvenil erat brain. Neurosci Lett 654:93–98. CrossRefPubMedGoogle Scholar
  63. Quansah E, Ruiz-Rodado V, Grootveld M, Probert F, Zetterström TSC (2017b) 1H NMR-based metabolomics reveals neurochemical alterations in the brain of adolescent rats following acute methylphenidate administration. Neurochem Int 108:109–120. CrossRefPubMedGoogle Scholar
  64. Ramirez MR, Muraro F, Zylbersztejn DS, Abel CR, Arteni NS, Lavinsky D, Netto CA, Trindade VMT (2003) Neonatal hypoxiaischemia reduces ganglioside, phospholipid and cholesterol contents in the rat hippocampus. Neurosci Res 46(3):339–347. CrossRefPubMedGoogle Scholar
  65. Réus GZ, Scaini G, Furlanetto CB, Morais MO, Jeremias IC, Mello Santos LM et al (2013) Methylphenidate treatment leads to abnor malities on Krebs cycle enzymes in the brain of young and adult rats. Neurotox Res 24(2):251–257. CrossRefPubMedGoogle Scholar
  66. Réus GZ, Scaini G, Titus SE, Furlanetto CB, Wessler LB, Ferreira GK, Gonçalves CL, Jeremias GC, Quevedo J, Streck EL (2015) Methylphenidate increases glucose uptake in the brain of young and adult rats. Pharmacol Rep 67(5):1033–1040. CrossRefPubMedGoogle Scholar
  67. Rice D, Barone S Jr (2000) Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect 108(s3):511–533. CrossRefPubMedPubMedCentralGoogle Scholar
  68. Röschlau P, Bernt E, Gruber W (1974) Cholesterol and esterified cholesterol, in: Bergmeyer, H.U., Gawehn, K. (Eds.), Methods of Enzymatic Analysis (Second English Edition): Academic, New York, pp. 1890-1893Google Scholar
  69. Sadasivan S, Pond BB, Pani AK, Qu C, Jiao Y, Smeyne RJ (2012) Methylphenidate exposure induces dopamine neuron loss and activation of microglia in the basal ganglia of mice. PLoS One 7(3):e33693. CrossRefPubMedPubMedCentralGoogle Scholar
  70. Schmitz F, Scherer EB, Machado FR, da Cunha AA, Tagliari B, Netto A, Wyse AT (2012a) Methylphenidate induces lipid and protein damage in prefrontal cortex, but not in cerebellum, striatum, and hippocampus of juvenile rats. Metab Brain Dis 27(4):605–612. CrossRefPubMedGoogle Scholar
  71. Schmitz F, Scherer EB, da Cunha MJ, da Cunha AA, Lima DD, Delwing D et al (2012b) Chronic methylphenidate administration alters antioxidant defenses and butyrylcholinesterase activity in blood of juvenile rats. Mol Cell Biochem 36:281–288CrossRefGoogle Scholar
  72. Schmitz F, Pierozan P, Rodrigues AF, Biasibetti H, Grunevald M, Pettenuzzo LF, Scaini G, Streck EL, Netto CA, Wyse ATS (2016a) Methylphenidate causes behavioral impairments and neuron and astrocyte loss in the hippocampus of juvenile rats. Mol Neurobiol 54(6):4201–4216. CrossRefPubMedGoogle Scholar
  73. Schmitz F, Pierozan P, Rodrigues AF, Biasibetti H, Grings M, Zanotto B, Coelho DM, Vargas CR, Leipnitz G, Wyse ATS (2016b) Methylphenidate decreases ATP levels and impairs glutamate uptake and Na+,K+-ATPase activity in juvenile rat hippocampus. Mol Neurobiol 54(10):7796–7807. CrossRefPubMedGoogle Scholar
  74. Schmitz F, Pierozan P, Rodrigues AF, Biasibetti H, Coelho DM, Mussulini BH, Pereira MS, Parisi MM, Barbé-Tuana F, Oliveira DL, Vargas CR, Wyse AT (2016c) Chronic treatment with a clinically relevant dose of methylphenidate increases glutamate levels in cerebrospinal fluid and impairs glutamatergic homeostasis in prefrontal cortex of juvenile rats. Mol Neurobiol 53:2385–2396Google Scholar
  75. Schneider JS, Roeltgen DP, Mancall EL, Chapas-Crilly J, Rothblat DS, Tatarian GT (1998) Parkinson’s disease. Improved function with GM1 ganglioside treatment in a randomized placebo-controlled study. Neurology 50(6):1630–1636. CrossRefPubMedGoogle Scholar
  76. She JQ, Wang M, Zhu DM, Sun LG, Ruan DY (2005) Effect of ganglioside on synaptic plasticity of hippocampus in lead-exposed rats in vivo. Brain Res 1060(1-2):162–116. CrossRefPubMedGoogle Scholar
  77. Sihag RK, Inagaki M, Yamaguchi T, Shea TB, Pant HC (2007) Role of phosphorylation on the structural dynamics and function of types III and IV intermediate filaments. Exp Cell Res 313(10):2098–2109. CrossRefPubMedPubMedCentralGoogle Scholar
  78. Souza RP, Soares EC, Rosa DV, Souza BR, Gomes KM, Valvassori SS, Réus GZ, Inácio CG, Martins MR, Gomez MV, Quevedo J, Romano-Silva MA (2009) Cerebral DARPP-32 expression after methylphenidate administration in young and adult rats. Int J Dev Neurosci 27(1):1–7. CrossRefPubMedGoogle Scholar
  79. Sowell ER, Peterson BS, Thompson PM, Welcome SE, Henkenius AL, Toga AW (2003) Mapping cortical change across the human life spa. Nat Neurosci 6(3):309–315. CrossRefPubMedGoogle Scholar
  80. Strack S, Westphal RS, Colbran RJ, Ebner FF, Wadzinski BE (1997) Protein serine/threonine phosphatase 1 and 2A associate with and dephosphorylate neurofilaments. Brain Res Mol Brain Res 49(1-2):15–28. CrossRefPubMedGoogle Scholar
  81. Svennerholm L (1957) Quantitative estimation of sialic acids a colorimetric resorcinol-hydrochloric acid method. Biochim Biophys Acta 24(3):604–611. CrossRefPubMedGoogle Scholar
  82. Svennerholm L (1963) Chromathographic separation of human brain gangliosides. J Neurochem 10(9):613–623. CrossRefPubMedGoogle Scholar
  83. Svenningsson P, Tzavara ET, Carruthers R, Rachleff I, Wattler S, Nehls M, McKinzie DL, Fienberg AA, Nomikos GG, Greengard P (2003) Diverse psychotomimetics act through a common signaling pathway. Science 302(5649):1412–1415. CrossRefPubMedGoogle Scholar
  84. Trindade VMT, Perry ML, Bernard EA (1992) Gangliosides and sialoproteins in hypothalamus of normal, postnatal, and pre-and postnatal protein undernourished rats. J Neurol Sci 107(1):93–97. CrossRefPubMedGoogle Scholar
  85. Trindade VMT, Brusque AM, Raasch JR, Pettenuzzo LE, Rocha HP, Wannmacher CM, Wajner M (2002) Ganglioside alterations in the central nervous system of rats chronically injected with methylmalonic and propionic acids. Metab Brain Dis 17(2):93–102. CrossRefPubMedGoogle Scholar
  86. Vannucci RC (1990) Experimental biology of hypoxia−/ischemia: relation to perinatal brain damage. Pediatr Res 27(4):317–356. CrossRefPubMedGoogle Scholar
  87. Veeranna GJ, Amin ND, Ahn NG, Jaffe H, Winters CA, Grant P, Pant HC (1998) Mitogen-activated protein kinases (Erk1,2) phosphorylate lys-ser-pro (KSP) repeats in neurofilament proteins NF-H and NF-M. J Neurosci 18(11):4008–4021CrossRefPubMedGoogle Scholar
  88. Volkow ND, Wang GJ, Fowler JS, Logan J, Gerasimov M, Maynard L, Ding Y, Gatley SJ, Gifford A, Franseschi D (2001) Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain. J Neurosci 21:1–5CrossRefGoogle Scholar
  89. Zanatta L, Goulart PB, Gonçalves R, Pierozan P, Winkelmann-Duarte EC, Woehl VM, Pessoa-Pureur R, Silva FR, Zamoner A (2012) 1α,25-dihydroxyvitamin D(3) mechanism of action: modulation of L-type calcium channels leading to calcium uptake and intermediate filament phosphorylation in cerebral cortex of young rats. Biochim Biophys Acta 1823(10):1708–1719. CrossRefPubMedGoogle Scholar
  90. Zhu Q, Couillard-Després S, Julien JP (1997) Delayed maturation of regenerating myelinated axons in mice lacking neurofilaments. Exp Neurol 148(1):299–316. CrossRefPubMedGoogle Scholar
  91. Zito JM, Safer DJ, dos Reis S, Gardner JF, Boles M, Lynch F (2000) Trends in the prescribing of psychotropic medications to preschoolers. JAMA 283(8):1025–1030. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Felipe Schmitz
    • 1
  • Paula Pierozan
    • 2
  • Helena Biasibetti-Brendler
    • 1
  • Fernanda Silva Ferreira
    • 1
  • Fernanda dos Santos Petry
    • 3
  • Vera Maria Treis Trindade
    • 1
    • 3
  • Regina Pessoa-Pureur
    • 1
    • 4
  • Angela T. S. Wyse
    • 1
    • 2
  1. 1.Programa de Pós-Graduação em Ciências Biológicas: BioquímicaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Laboratório de Neuroproteção e Doenças Metabólicas, Departamento de Bioquímica, Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  3. 3.Laboratório de Bioquímica e Biologia Celular de Lipídios, Departamento de Bioquímica, Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  4. 4.Laboratório do Citoesqueleto, Departamento de Bioquímica, Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do SulPorto AlegreBrazil

Personalised recommendations