title: Adolescent Risperidone treatment alters protein expression associated with protein trafficking and cellular metabolism in the adult rat prefrontal cortex.
abstract: The prefrontal cortex (PFC) is associated with mental health illnesses including schizophrenia, depression, bipolar disorder, and autism spectrum disorders. It richly expresses neuroreceptors which are the target for antipsychotics. However, as the precise mechanism of action of antipsychotic medications is not known, proteomic studies of the effects of antipsychotic drugs on the brain are warranted. In the current study, we aimed to characterize protein expression in the adult rodent PFC (n = 5 per group) following low-dose treatment with Risperidone or saline in adolescence (postnatal days 34-47). The PFC was examined by triplicate 1 h runs of label-free LC-MS/MS. The raw mass spectral data were analyzed with the MaxQuant(TM) software. Statistical analysis was carried out using SAS® Version 9.1. Pathway and functional analysis was performed with IngenuityPathway Analysis and in the Database for Annotation, Visualization and Integrated Discovery (DAVID), respectively, the most implicated pathways were found to be related to mitochondrial function, protein trafficking, and the cytoskeleton. This report adds to the current repertoire of data available concerning the effects of antipsychotic drugs on the brain and sheds light on their biological mechanisms. The MS data have been deposited with the ProteomeXchange Consortium with dataset identifier PXD000480.
authors.affiliation: Department of Psychiatry, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland.
authors.forename: Lorna A
authors.initials: LA
authors.lastname: Farrelly
authors.forename: Patrick
authors.initials: P
authors.lastname: Dicker
authors.forename: Kieran
authors.initials: K
authors.lastname: Wynne
authors.forename: Jane
authors.initials: J
authors.lastname: English
authors.forename: Gerard
authors.initials: G
authors.lastname: Cagney
authors.forename: Melanie
authors.initials: M
authors.lastname: Föcking
authors.forename: David R
authors.initials: DR
authors.lastname: Cotter
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002468:Cell Physiological Phenomena / Q000187:drug effects; D002853:Chromatography, Liquid / Q000379:methods; D030562:Databases, Protein; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D018967:Risperidone / Q000494:pharmacology*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D014150:Antipsychotic Agents; D020543:Proteome; D018967:Risperidone
keywords: Antipsychotics; Biomedicine; LC-MS/MS; Prefrontal cortex; Risperidone