Proteomic signatures of Psychosocial Stress and Western Diet- driven Mitochondrial Dysfunction in Frontal Cortex and Hippocampus

ABSTRACT: Chronic Stress and Western diet are major risk factors for affective disorders, however their biological interactions remain unclear. This study examined the neurochemical, mitochondrial, metabolic, behavioural and proteomic effects of a chronic stress paradigm (2h/day for 2 weeks) in male C57bl/6 mice fed either a control or Western diet for 20 weeks. This study showed that a Western diet induced metabolic dysfunction and depressive-like symptoms (reduce sucrose preference), but had minimal impact of frontal cortex or hippocampal mitochondrial or neurochemical measures. In contrast, chronic stress produced anxiety-like behaviour (via open field test measures), frontal cortex reductions in BDNF and GABA, elevated Glutamate and marked mitochondrial dysfunction. When combined, mice showed depressive-like behaviours despite similar neurochemical changes to that observed with stress alone. Proteomic analyses showed stress-related disruption of mitochondrial, synaptogenesis and NRF2 pathways, as well as adaptive responses to stress or Western diet that were reversed to maladaptive under co-morbid conditions. Finding implicate failed mitochondrial and synaptic adaptations in frontal cortex as key mechanisms linking stress-diet interactions to affective pathology.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Chul-Kyu Kim  

LAB HEAD: Eugene Du Toit

PROVIDER: PXD074187 | Pride | 2026-05-25

REPOSITORIES: Pride