title: Methylphenidate Decreases ATP Levels and Impairs Glutamate Uptake and Na+,K+-ATPase Activity in Juvenile Rat Hippocampus.
abstract: The study of the long-term neurological consequences of early exposure with methylphenidate (MPH) is very important since this psychostimulant has been widely misused by children and adolescents who do not meet full diagnostic criteria for ADHD. The aim of this study was to examine the effect of early chronic exposure with MPH on amino acids profile, glutamatergic and Na+,K+-ATPase homeostasis, as well as redox and energy status in the hippocampus of juvenile rats. Wistar male rats received intraperitoneal injections of MPH (2.0 mg/kg) or saline solution (controls), once a day, from the 15th to the 45th day of age. Results showed that MPH altered amino acid profile in the hippocampus, decreasing glutamine levels. Glutamate uptake and Na+,K+-ATPase activity were decreased after chronic MPH exposure in the hippocampus of rats. No changes were observed in the immunocontents of glutamate transporters (GLAST and GLT-1), and catalytic subunits of Na+,K+-ATPase (α1, α2, and α3), as well as redox status. Moreover, MPH provoked a decrease in ATP levels in the hippocampus of chronically exposed rats, while citrate synthase, succinate dehydrogenase, respiratory chain complexes activities (II, II-III, and IV), as well as mitochondrial mass and mitochondrial membrane potential were not altered. Taken together, our results suggest that chronic MPH exposure at early age impairs glutamate uptake and Na+,K+-ATPase activity probably by decreasing in ATP levels observed in rat hippocampus.
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: Schmitz
authors.affiliation: Laboratório de Neuroproteção e Doenças Metabólicas, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Paula
authors.initials: P
authors.lastname: Pierozan
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: André F
authors.initials: AF
authors.lastname: Rodrigues
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Helena
authors.initials: H
authors.lastname: Biasibetti
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Mateus
authors.initials: M
authors.lastname: Grings
authors.affiliation: Laboratório de Neuroproteção e Doenças Metabólicas, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Zanotto
authors.affiliation: Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Daniella M
authors.initials: DM
authors.lastname: Coelho
authors.affiliation: Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Carmen R
authors.initials: CR
authors.lastname: Vargas
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Laboratório de Neuroproteção e Doenças Metabólicas, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Guilhian
authors.initials: G
authors.lastname: Leipnitz
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. wyse@ufrgs.br.|Laboratório de Neuroproteção e Doenças Metabólicas, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. wyse@ufrgs.br.|Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, CEP 90035-003, Brazil. wyse@ufrgs.br.
authors.forename: Angela T S
authors.initials: ATS
authors.lastname: Wyse
mesh_terms: D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase
keywords: ATP levels; Amino acid levels; Glutamatergic homeostasis; Methylphenidate; Mitochondrial function; Na+,K+-ATPase