Hippocampal ALKBH5 Contributes to Depression-like Behaviors in a Mouse Model of Inflammatory Pain.

BACKGROUND

Chronic pain and depressive symptoms frequently coexist and mutually reinforce each other, severely compromising patients' quality of life, yet the underlying central molecular mechanisms remain poorly understood. ALKBH5, an m6A demethylase, has been implicated in the regulation function of central nervous system. However, whether ALKBH5 contributes to depression-like behaviors induced by chronic inflammatory pain remains unknown.

METHODS

The Complete Freund's adjuvant (CFA)-induced inflammatory pain model was employed in this study. ALKBH5 expression and behavioral performances were examined in CFA-treated mice. To further validate the role of hippocampal ALKBH5 in this model, adeno-associated virus (AAV)-mediated shRNA was delivered to knock down ALKB5 in the hippocampus.

RESULTS

ALKBH5 protein levels were significantly unregulated in the hippocampus of CFA mice. Adenovirus-mediated knockdown of hippocampal ALKBH5 markedly alleviated CFA-induced depressive-like behaviors, possibly due to the reduced expression of iNOS.

CONCLUSION

our findings identify hippocampal ALKBH5 as a key regulator of depression-like behaviors in chronic inflammatory pain and suggest that targeting ALKBH5 may provide a novel therapeutic strategy for alleviating affective disorders associated with chronic pain.