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

Abstract

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.

Keywords

Methylphenidate Cytoskeleton Intermediate filaments Cholesterol Gangliosides Phospholipids 

Abbreviations

ADHD

Attention deficit hyperactivity disorder

CNS

Central nervous system

GFAP

Glial fibrillary acidic protein

IFs

Intermediate filaments

KSP

Lysine-serine-proline

MPH

Methylphenidate

NF

Neurofilament

NFH

High molecular weight neurofilament subunit

NFL

Light molecular weight neurofilament subunit

NFM

Middle molecular weight neurofilament subunit

PP1

Protein phosphatase 1

PP2A

Protein phosphatase 2A

PP2B

Calcineurin

Notes

Acknowledgements

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.

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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

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