Curcumin relieves corticosterone‐induced behaviour deficits via PGC‐1α‐mediated mitochondrial biogenesis and mitophagy

Abstract

AbstractCurcumin (CUR), an FDA‐approved natural product, has been found to be clinically effective in treating depression. However, the underlying mechanism remains elusive. PGC‐1α is a key factor in regulating mitochondrial health and depression. This study randomly divided C57BL/6 mice or cultured hippocampal neurons into four groups: CON, CORT, CORT + CUR and CORT + CUR + SR18292. The present study demonstrated that CUR was effective in suppressing CORT‐induced depressive‐like behaviour, as well as improving anxiety‐like behaviour and cognitive function. CUR was found to be effective in preventing oxidative stress induced by corticosterone (CORT), as evidenced by the restoration of Nrf2, NQO‐1, HO‐1, GCLC, SOD‐1 and DHE levels in cells. CUR inhibited the CORT‐induced perinuclear accumulation of mitochondria in vitro. Furthermore, CUR promoted mitochondrial biogenesis, potentially reversing the effect of CORT on NRF1, TFAM, PGC‐1α and the relative MT‐CO1/SDH‐A ratio. Lastly, the treatment of CUR normalized the CORT‐hindered mitophagy by upregulating the protein level of NIX, Beclin‐1, PINK1, Parkin and LC3II/LC3I, and enhancing the relative mt‐Keima signal. The protective effect of CUR was entirely negated by SR18292. CUR could regulate oxidative stress, mitochondrial biogenesis and mitophagy via PGC‐1α to achieve an anti‐depressive‐like function. This study would contribute to a greater understanding of how CUR alleviates depressive symptoms.