Abstract
Emerging evidence suggests that hierarchical status provides vulnerability to develop stress-induced depression. Energy metabolic changes in the nucleus accumbens (NAc) were recently related to hierarchical status and vulnerability to develop depression-like behavior. Acetyl-L-carnitine (LAC), a mitochondria-boosting supplement, has shown promising antidepressant-like effects opening therapeutic opportunities for restoring energy balance in depressed patients. We investigated the metabolic impact in the NAc of antidepressant LAC treatment in chronically-stressed mice using 1H-magnetic resonance spectroscopy (1H-MRS). High rank, but not low rank, mice, as assessed with the tube test, showed behavioral vulnerability to stress, supporting a higher susceptibility of high social rank mice to develop depressive-like behaviors. High rank mice also showed reduced levels of several energy-related metabolites in the NAc that were counteracted by LAC treatment. Therefore, we reveal a metabolic signature in the NAc for antidepressant-like effects of LAC in vulnerable mice characterized by restoration of stress-induced neuroenergetics alterations and lipid function.
Highlights
Depression is among the leading causes of disability worldwide, which reflects the current lack of understanding of its underlying mechanisms [1, 2]
We reveal a metabolic signature in the nucleus accumbens (NAc) for the antidepressant-like effects of LAC in vulnerable mice, characterized by restoration of stress-induced alterations in neuroenergetics and lipid function
In metabolites strongly loading in factor 1, we found that the observed stress effect was mainly carried by changes in Tau (p
Summary
Emerging evidence suggests that hierarchical status may provide vulnerability to develop stressinduced depression. Energy metabolism in the nucleus accumbens (NAc) was recently related to hierarchical status and vulnerability to develop depression-like behavior. Acetyl-L-carnitine (LAC), a mitochondria-boosting supplement, has shown promising antidepressant-like effects opening promising therapeutic strategies for restoring energy balance in depressed patients. We investigated the metabolic impact in the NAc of antidepressant LAC treatment in chronically stressed mice
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