Methylphenidate Exposing During Neurodevelopment Alters Amino Acid Profile, Astrocyte Marker and Glutamatergic Excitotoxicity in the Rat Striatum.

Autor: Schmitz F; Neuroprotection and Neurometabolic Diseases Laboratory (Wyse´S Lab), Department of Biochemistry, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.; Graduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Durán-Carabali LE; Graduate Program in Biological Sciences: Physiology, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. Luzeled67@gmail.com., Rieder AS; Neuroprotection and Neurometabolic Diseases Laboratory (Wyse´S Lab), Department of Biochemistry, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.; Graduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Silveira JS; Neuroprotection and Neurometabolic Diseases Laboratory (Wyse´S Lab), Department of Biochemistry, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.; Graduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Ramires Junior OV; Neuroprotection and Neurometabolic Diseases Laboratory (Wyse´S Lab), Department of Biochemistry, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.; Graduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Bobermin LD; Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Quincozes-Santos A; Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Alves VS; Laboratory of Immunophysiology, Biophysics, Institute Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Coutinho-Silva R; Laboratory of Immunophysiology, Biophysics, Institute Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Savio LEB; Laboratory of Immunophysiology, Biophysics, Institute Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Coelho DM; Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil., Vargas CR; Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil., Netto CA; Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Wyse ATS; Neuroprotection and Neurometabolic Diseases Laboratory (Wyse´S Lab), Department of Biochemistry, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. wyse@ufrgs.br.; Department of Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. wyse@ufrgs.br.
Jazyk: angličtina
Zdroj: Neurotoxicity research [Neurotox Res] 2024 Aug 27; Vol. 42 (5), pp. 39. Date of Electronic Publication: 2024 Aug 27.
DOI: 10.1007/s12640-024-00718-y
Abstrakt: There is a public health concern about the use of methylphenidate (MPH) since the higher prescription for young individuals and non-clinical purposes is addressed to the limited understanding of its neurochemical and psychiatric consequences. This study aimed to evaluate the impact of early and chronic MPH treatment on the striatum focusing on amino acid profile, glutamatergic excitotoxicity, redox status, neuroinflammation and glial cell responses. Male Wistar rats were treated with MPH (2.0 mg/kg) or saline solution from the 15th to the 44th postnatal day. Biochemical and histological analyses were conducted after the last administration. MPH altered the amino acid profile in the striatum, increasing glutamate and ornithine levels, while decreasing the levels of serine, phenylalanine, and branched-chain amino acids (leucine, valine, and isoleucine). Glutamate uptake and Na + ,K + -ATPase activity were decreased in the striatum of MPH-treated rats as well as increased ATP levels, as indicator of glutamatergic excitotoxicity. Moreover, MPH caused lipid peroxidation and nitrative stress, increased TNF alpha expression, and induced high levels of astrocytes, and led to a decrease in BDNF levels. In summary, our results suggest that chronic early-age treatment with MPH induces parallel activation of damage-associated pathways in the striatum and increases its vulnerability during the juvenile period. In addition, data presented here contribute to shedding light on the mechanisms underlying MPH-induced striatal damage and its potential implications for neurodevelopmental disorders.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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