Amb motiu del tancament d'estiu, la validació de documents es reprendrà a partir del 28 d'agost de 2026. Disculpeu les molèsties.
Con motivo del cierre de verano, la validación de documentos se reanudará a partir del 28 de agosto de 2026. Disculpad las molestias
Due to the summer closure, document validation will resume starting August 28, 2026. We apologize for any inconvenience.

Files

676966.pdf (671.87 KB)

Document type

Article

Version

Published version

Publication date

2018-01

Publication license

cc-by (c) Garcia Cerro, Susana et al., 2018
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/184557

Different modulation of RPS6 phosphorylation by risperidone in striatal cells sub populations: involvement of the mTOR pathway in antipsychotic-induced extrapyramidal symptoms in mice

Journal Title

Authors

Director/Tutor

Journal ISSN

Volume Title

Related resource

https://doi.org/10.4172/Neuropsychiatry.1000436

Abstract

Objective: Acute extrapyramidal symptoms (EPS) are frequent and serious adverse reactions to antipsychotic (AP) drugs. Although the proposed mechanism is an excessive blockade of dopamine D2 receptors in the striatopallidal pathway of the striatum, previous studies implicated the mTOR pathway in the susceptibility to EPS. The objective of the present study is to analyze the mTOR-mediated response to risperidone in subpopulations of striatal neurons and its relationship to risperidone-induced motor side effects. Methods: Two mouse strains (A/J and DBA/2J) with different susceptibility to developing EPS were treated with risperidone 1 mg/kg for three consecutive days. Here we monitored, by double labeling immunohistochemistry, ribosomal protein S6 (rpS6) phosphorylation (Ser235/236 and Ser244/247 sites), a marker of mTOR signaling, in the striatonigral pathway (D1-medium spiny neurons (MSNs)), the striatopallidal pathway (D2-MSNs) and striatal cholinergic interneurons. Results: We found that EPS-resistant DBA/2J mice show higher baseline levels of phosphoactivated rpS6 protein in striatal MSNs, compared with EPS-prone A/J mice. Moreover, risperidone differentially targeted rpS6 phosphorylation in direct and indirect pathway neurons in a strain-specific manner: a significant decrease in the phosphorylation of rpS6 at Ser235/236 and Ser240/244 in DRD1-MSNs EPS-resistant DBA/2J mice after; and a significant increase of phospho-Ser235/236-rpS6 in the striatopallidal pathway of the EPS-prone A/J mice in response to risperidone. Conclusions: Our results reveal the vital role of genetic background in the response to risperidone, and point to the mTOR pathway as an important factor in EPS susceptibility. Keywords: Schizophrenia, Antipsychotic, Risperidone, Extrapyramidal symptoms. mTOR pathway, Striatum, Medium spiny neurons

Subject

Esquizofrènia, Antipsicòtics, Fosforilació, Malaltia de Parkinson

Subject (English)

Schizophrenia, Antipsychotic drugs, Phosphorylation, Parkinson's disease

Citation

Collections

Articles publicats en revistes (Fonaments Clínics)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut de Neurociències (UBNeuro))

Citation

GARCÍA CERRO, Susana, et al. Different modulation of RPS6 phosphorylation by risperidone in striatal cells sub populations: involvement of the mTOR pathway in antipsychotic-induced extrapyramidal symptoms in mice. Neuropsychiatry. 2018. Vol. 8, num. 3, pags. 1083-1093. ISSN 1758-2008. [consulted: 19 of August of 2026]. Available at: https://hdl.handle.net/2445/184557

Export metadata

JSON - METS

Share record