Analysis of networks in the dorsolateral prefrontal cortex in chronic schizophrenia: Relevance of altered immune response.

Front Pharmacol

Psiquiatria Molecular, Parc Sanitari Sant Joan de Déu, Institut de Recerca Sant Joan de Déu, Sant Boi de Llobregat, Spain.

Published: March 2023

AI Article Synopsis

  • The dorsolateral prefrontal cortex (DLPFC) is key to cognitive abilities and negative symptoms in schizophrenia, but little is known about its protein networks in this condition.
  • A study analyzed protein changes in the DLPFC of individuals with schizophrenia versus unaffected individuals, identifying 1989 proteins, with 43 significantly altered linked to important biological processes like immune response and intracellular transport.
  • Findings highlight a downregulation in pathways related to MHC class II antigen presentation and vesicle-mediated transport, emphasizing RAB7A as a central player in this network that may be targeted for new schizophrenia treatments to enhance cognitive and negative symptoms.

Article Abstract

The dorsolateral prefrontal cortex (DLPFC) has a crucial role in cognitive functioning and negative symptoms in schizophrenia. However, limited information of altered protein networks is available in this region in schizophrenia. We performed a proteomic analysis using single-shot liquid chromatography-tandem mass spectrometry of grey matter of postmortem DLPFC in chronic schizophrenia subjects (n = 20) and unaffected subjects (n = 20) followed by bioinformatic analysis to identify altered protein networks in schizophrenia (PXD024939 identifier in ProteomeXchange repository). Our results displayed a proteome profile in the DLPFC of 1989 proteins. 43 proteins were found significantly altered in schizophrenia. Analysis of this panel showed an enrichment of biological processes implicated in vesicle-mediated transport, processing and antigen presentation MHC class II, intracellular transport and selenium metabolism. The enriched identified pathways were MHC class II antigen presentation, vesicle-mediated transport, Golgi ER retrograde transport, Nef mediated CD8 downregulation and the immune system. All these enriched categories were found to be downregulated. Furthermore, our network analyses showed crosstalk between proteins involved in MHC class II antigen presentation, membrane trafficking, Golgi-to-ER retrograde transport, Nef-mediated CD8 downregulation and the immune system with only one module built by 13 proteins. RAB7A showed eight interactions with proteins of all these pathways. Our results provide an altered molecular network involved in immune response in the DLPFC in schizophrenia with a central role of RAB7A. These results suggest that RAB7A or other proteins of this network could be potential targets for novel pharmacological strategies in schizophrenia for improving cognitive and negative symptoms.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076656PMC
http://dx.doi.org/10.3389/fphar.2023.1003557DOI Listing

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