Long-chain acyl-CoenzymeA synthetase-2 mRNA: increased cerebral cortex expression in an animal model of depression.

Long chain acyl-CoA synthetase-2 (LACS-2) is a critical enzyme involved in fatty acid metabolism in the brain. The disruption of fatty acid composition and metabolism has been hypothesized to play a role in major depression. Rats exposed to the learned helplessness paradigm, an animal model of depression, were classified as either learned helpless (LH, n=8) or non-learned helpless (nLH, n=8) on the basis of escape performance. Quantitative in situ hybridization analysis was used to determine LACS-2 mRNA levels in the frontal cortex of LH, nLH and normal control rats (n=8). LACS-2 mRNA expression throughout the frontal cortex was consistently higher in LH compared to controls in all 49 regions sampled. Upregulation of LACS-2 mRNA was most prominent in the LH group, followed by nLH and controls, which exhibiting lowest expression levels. This trend was observed in 84% of the regions examined. Statistically significant increases in the LH group vs. controls (p<0.05) were seen in nine different brain regions. The results demonstrate that LACS-2 expression is significantly upregulated in distinct regions of the frontal cortex in LH rats relative to controls. This suggests that fatty acid metabolism may be altered in the learned helplessness model.