Dataset Information

Prefrontal cortical synaptoproteome profile combined with machine learning predict resilience towards chronic social isolation in rats

ABSTRACT: Chronic social isolation (CSIS), an animal model of depression, generates two stress-response phenotypes: CSIS-resilient and CSIS-susceptible. However, the molecular mechanism underlying resilience to CSIS remains unclear. We aimed to investigate the prefrontal cortical synaptoproteome profile between CSIS-resilient, CSIS-susceptible and control rats in order to identify predictive proteins for the resilience phenotype. Comparison of CSIS-resilient versus CSIS-susceptible rats revealed downregulated glycolysis intermediate Aldoc and upregulated Cltc, Cam2a, Syn and Fasn proteins involved in neuronal transmission, synaptic vesicle trafficking and fatty acid synthesis. Comparison of CSIS-resilient and control rats revealed downregulated mitochondrial proteins Atp5f1b and Cs, and upregulated Prkcg, Slc17a7, and Sv2a proteins involved in signal transduction and synaptic trafficking. These proteins make the animal groups linearly separable, and 100% validation accuracy is achieved by standard machine learning models. In addition, we identified the most significant proteins for discriminating CSIS-resilient vs. CSIS-susceptible or control rats by using Support Vector Machine with greedy forward search and Random Forest, resulting in four panels of discriminative proteins. Proteomics-data-driven machine learning algorithms can provide a platform for accessing predictive features and provide additional insight into the molecular mechanisms of synaptic neurotransmission involved in stress resilience.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain

SUBMITTER: Dragana Filipovic

LAB HEAD: Dragana Filipović

PROVIDER: PXD047159 | Pride | 2024-04-23

REPOSITORIES: Pride

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Publications

Prefrontal cortical synaptoproteome profile combined with machine learning predicts resilience towards chronic social isolation in rats.

Filipović Dragana D Novak Božidar B Xiao Jinqiu J Tadić Predrag P Turck Christoph W CW

Journal of psychiatric research 20240221

Chronic social isolation (CSIS) of rats serves as an animal model of depression and generates CSIS-resilient and CSIS-susceptible phenotypes. We aimed to investigate the prefrontal cortical synaptoproteome profile of CSIS-resilient, CSIS-susceptible, and control rats to delineate biochemical pathways and predictive biomarker proteins characteristic for the resilient phenotype. A sucrose preference test was performed to distinguish rat phenotypes. Class separation and machine learning (ML) algori ...[more]

PMID: 38412784

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Project description:Some individuals show a discrepancy between cognition and the amount of neuropathological changes characteristic for Alzheimer’s disease (AD). This phenomenon has been referred to as ‘resilience’. The molecular and cellular underpinnings of resilience remain poorly understood. To obtain an unbiased understanding of the molecular changes underlying resilience, we investigated global changes in gene expression in the superior frontal gyrus of a cohort of cognitively and pathologically well-defined AD patients, resilient individuals and age-matched controls (n=11-12 per group). 897 genes were significantly altered between AD and control, 1121 between resilient and control and 6 between resilient and AD. Gene set enrichment analysis (GSEA) revealed that the expression of metallothionein (MT) and of genes related to mitochondrial processes was higher in the resilient donors. Weighted gene co-expression network analysis (WGCNA) identified gene modules related to the unfolded protein response, mitochondrial processes and synaptic signaling to be differentially associated with resilience or dementia. As changes in MT, mitochondria, heat shock proteins and the unfolded protein response (UPR) were the most pronounced changes in the GSEA and/or WGCNA, immunohistochemistry was used to further validate these processes. MT was significantly increased in astrocytes in resilient individuals. A higher proportion of the mitochondrial gene MT-CO1 was detected outside the cell body versus inside the cell body in the resilient compared to the control group and there were higher levels of heat shock protein 70 (HSP70) and X-box-binding protein 1 spliced (XBP1s), two proteins related to heat shock proteins and the UPR, in the AD donors. Finally, we show evidence for putative sex-specific alterations in resilience, including gene expression differences related to autophagy in females compared to males. Taken together, these results show possible mechanisms involving MTs, mitochondrial processes and the UPR by which individuals might maintain cognition despite the presence of AD pathology.

Dataset Information

Prefrontal cortical synaptoproteome profile combined with machine learning predict resilience towards chronic social isolation in rats

Publications

Prefrontal cortical synaptoproteome profile combined with machine learning predicts resilience towards chronic social isolation in rats.

Similar Datasets

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