Details

Autor(en) / Beteiligte

• Schmitz, Felipe
• Durán-Carabali, Luz Elena
• Rieder, Alessandra Schmitt
• Silveira, Josiane S.
• Ramires Junior, Osmar Vieira
• Bobermin, Larissa D.
• Quincozes-Santos, André
• Alves, Vinícius S.
• Coutinho-Silva, Robson
• Savio, Luiz Eduardo B.
• Coelho, Daniella M.
• Vargas, Carmen R.
• Netto, Carlos Alexandre
• Wyse, Angela T. S.

Titel

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

Ist Teil von

• Neurotoxicity research, 2024-08, Vol.42 (5), p.39

Ort / Verlag

New York: Springer US

Erscheinungsjahr

2024

Quelle

SpringerLink

Beschreibungen/Notizen

• 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. Graphical Abstract Graphical summary of the processes that were quantified throughout the investigations, highlighting the main effects of chronic methylphenidate exposure on crucial parameters for the proper functioning of the central nervous system. In summary, chronic MPH exposure at early age altered AA profile, impaired glutamate uptake and Na + ,K + -ATPase activity probably by lipid peroxidation/nitrative stress. Moreover, MPH increased TNF-α expression and astrocyte reactivity in the striatum of juvenile rats. Gln, glutamine; Glu, glutamate; MPH, methylphenidate; DA, dopamine; RNS; reactive nitrogen species; TNF-α: tumor necrosis factor alpha. Figure created in BioRender.com