Amino acid metabolic dysfunction revealed in the prefrontal cortex of a rat model of depression

Abstract

Major depressive disorder (MDD) is a debilitating mood disorder. However, the molecular mechanism(s) underlying depression remain largely unknown. Here, we applied a GC-MS-based metabonomic approach in the chronic unpredictable mild stress (CUMS) model, a well-established rodent model of depression, to investigate significant metabolic changes in the rat prefrontal cortex (PFC). Multivariate statistical analysis - including principal component analysis, partial least squares-discriminate analysis, and pair-wise orthogonal projections to latent structures discriminant - was applied to identify differential PFC metabolites between CUMS rats and healthy controls. As compared to healthy control rats, CUMS rats were characterized by lower levels of isoleucine and glycerol in combination with higher levels of N-acetylaspartate and β-alanine. These findings should provide insight into the pathophysiological mechanism(s) underlying MDD and preliminary leads relevant to diagnostic biomarker discovery for depression.

Keywords: Chronic unpredictable mild stress, CUMS; Depression, Major depressive disorder, MDD; Metabonomic, metabolomic; Prefrontal cortex, PFC.