Effects of chronic social stress on mitochondrial and mitochondrial-associated membrane protein networks in the mouse brain

ABSTRACT: Stressors challenge metabolic processes to adapt to ever-changing environmental conditions and herein, the brain is exceptionally amenable to change. Simultaneously, the high cerebral energy demands may render the brain particularly vulnerable to the metabolic consequences of psychological stress. Mitochondria are central organelles within energy metabolism, known to dynamically adjust function according to shifts in metabolic demands, and thus pivotal in the stress response. It is largely unclear how mitochondria respond to a psychological stressor and how mitochondria orchestrate their actions with other organelles, such as the endoplasmatic reticulum (ER). To address these questions we subjected male mice to chronic social defeat stress (CSD) and analyzed different subcellular brain fractions using label-free proteomics: mitochondrial associated membranes (MAMs), ER, and crude and pure mitochondrial fractions. Although insufficient to warrant a protein pathway analysis, we identified a few noteworthy differentially regulated proteins. These included decreased levels of SH3GL2 (SH3 Domain Containing GRB2 Like 2 or Endophilin 1) in the crude mitochondrial fraction of stressed mice, which may be related to impaired presynaptic calcium influx. In line, CACNA1A (Calcium Voltage-Gated Channel Subunit Alpha1 A) was absent in the pure mitochondrial fraction from CSD-exposed mice, a finding also suggestive of an impaired mitochondrial calcium flux. Then, in the MAM-fraction we observed an absence of HK3 (hexokinase 3) in CSD-treated mice, which may be linked to the CSD-induced cerebral hyperglycemia reported previously. Although verification is still required, our findings revealed a number of differentially expressed proteins possibly critical in the metabolic response to chronic stress.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Sabine Arndt  

LAB HEAD: Stefan Tenzer

PROVIDER: PXD015983 | Pride | 2022-10-13

REPOSITORIES: Pride