The neuroprotection of electro-acupuncture via the PGC-1α/TFAM pathway in transient focal cerebral ischemia rats

Abstract

ATP depletion is one of the pathological bases in cerebral ischemia. Electro-acupuncture (EA) is widely used in clinical practice for ischemia. However, the mechanism of EA remains unclear. The purpose of this study was to investigate whether EA could activate the AMPK/PGC-1α/TFAM signaling pathway and, consequently, increase the preservation of ATP in rats with ischemia. In this study, 48 rats were randomly divided into four groups as a sham-operation control group (sham group), a middle cerebral artery occlusion group (MCAO group), an EA group, and an EA group blocked by the AMPK inhibitor compound C (EA + CC group) (N = 12/group). The rats of the EA group and EA + CC group received the EA treatment for 7 days. The rats that belonged in the two remaining groups were only grasped in the same condition. Then, their brain tissues were collected for further detection. When compared with other groups, EA significantly reduced neurological deficits score and increased motor function. The cerebral infarction volume was significantly reduced in the EA group according to TTC staining. With western blot, we found that EA improved the ratio of p-AMPKα/AMPKα (P < 0.05), however, there is no difference between the MCAO group and sham group (P > 0.05). In addition, EA also increased the expression of PGC-1α and TFAM (all P < 0.05). By Elisa, we observed that EA increased the preservation of ATP (P < 0.05) and mitochondrial respiratory enzymes, including Complex I (P < 0.05), Complex IV (P < 0.05), but not Complex III (P > 0.05). In summary, we conclude that EA may protect against ischemic damage in MCAO rats, improve the preservation of ATP and mitochondrial respiratory enzymes. This effect may be positively regulated by the activation of the PGC-1α/TFAM signaling pathway.

Arsenic-Induced, Mitochondria-Mediated Apoptosis Is Associated with Decreased Peroxisome Proliferator-Activated Receptor γ Coactivator α in Rat Brains

“…Then, we analyzed the effect of arsenic on the mitochondrial apoptosis pathway and PGC-1α expression in this study; the result showed that there was a negative correlation between apoptosis and PGC-1α, which suggested that PGC-1α plays an important role in arsenic-induced hippocampal neuronal cell apoptosis. Previous studies have shown that brain ATP content is regulated by PGC-1α, and the decrease of PGC-1α reduces the content of ATP [ 46 , 47 , 48 ]. In this study, there was positive correlation between PGC-1α and ATP contents.…”