Exploring the metabolomic profile of cerebellum after exposure to acute stress

Abstract

Psychological stress and stress-related disorders constitute a major health problem in modern societies. Although the brain circuits involved in emotional processing are intensively studied, little is known about the implication of cerebellum in stress responses whereas the molecular changes induced by stress exposure in cerebellum remain largely unexplored. Here, we investigated the effects of acute stress exposure on mouse cerebellum. We used a forced swim test (FST) paradigm as an acute stressor. We then analyzed the cerebellar metabolomic profiles of stressed (n = 11) versus control (n = 11) male CD1 mice by a Nuclear Magnetic Resonance (NMR)-based, untargeted metabolomics approach. Our results showed altered levels of 19 out of the 47 annotated metabolites, which are implicated in neurotransmission and N-acetylaspartic acid (NAA) turnover, as well as in energy and purine/pyrimidine metabolism. We also correlated individual metabolite levels with FST behavioral parameters, and reported associations between FST readouts and levels of 4 metabolites. This work indicates an altered metabolomic signature after acute stress in the cerebellum and highlights a previously unexplored involvement of cerebellum in stress responses.