Chronic stress leads to epigenetic dysregulation of neuropeptide-Y and cannabinoid CB1 receptor in the mouse cingulate cortex.

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“Persistent stress triggers a variety of mechanisms, which may ultimately lead to the occurrence of anxiety- and depression-related disorders.

Epigenetic modifications represent a mechanism by which chronic stress mediates long-term effects. Here, we analyzed brain tissue from mice exposed to chronic unpredictable stress (CUS), which induced impaired emotional and nociceptive behaviors.

As endocannabinoid (eCB) and neuropeptide-Y (Npy) systems modulate emotional processes, we hypothesized that CUS may affect these systems through epigenetic mechanisms.

We found reduced Npy expression and Npy type 1 receptor (Npy1r) signaling, and decreased expression of the cannabinoid type 1 receptor (CB1) in the cingulate cortex of CUS mice specifically in low CB1-expressing neurons.

Our findings suggest that epigenetic alterations in the Npy and CB1 genes represent one of the potential mechanisms contributing to the emotional imbalance induced by CUS in mice, and that the Npy and eCB systems may represent therapeutic targets for the treatment of psychopathologies associated with or triggered by chronic stress states.”

https://www.ncbi.nlm.nih.gov/pubmed/27737789

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