Changes in Mitochondria-Associated Protein Expression and Mitochondrial Function in Response to 2 Weeks of Enriched Environment Training After Cerebral Ischaemia-Reperfusion Injury.

Abstract

An enriched environment (EE) can stimulate the recovery of neurological function following a cerebral ischaemia-reperfusion injury; however, the impact of EE's on mitochondrial function has been insufficiently studied. Our research aimed to assess whether EE's therapeutic impact involved the enhancement of mitochondrial dysfunction. Following 2 weeks of EE training, we tested both mitochondrial function and mitochondria-associated protein expression within the cerebral cortex following cerebral ischaemia-reperfusion injury. We subjected Sprague-Dawley rats to transient focal cerebral ischaemia and categorized the rats into three separate groups, i.e. an enriched environment (EE) group, a standard condition (SC) group and a sham control group (no middle cerebral artery embolization). The rats within the EE group were raised in enriched conditions for 2 weeks, while the rats within the SC group, in comparison, were reared in standard conditions for 2 weeks. After 2 weeks, the cerebral cortices of the rats were removed. We then measured a series of indices, i.e. the protein expression of peroxisome proliferator-activated receptor gamma coactivator (PGC-1α), nuclear respiratory factor-1 (NRF-1), mitochondrial transcription factor A (TFAM) and mitochondrial protein cytochrome C oxidase subunit IV (COX IV). Furthermore, the number of mitochondria was evaluated through electron microscopy.EE upregulated the protein expression of PGC-1α, NRF-1 as well as TFAM, which function as the master regulators of mitochondrial biogenesis, in comparison with the SC group. The EE group's COX IV protein expression also exhibited an increase. Moreover, the amount of mitochondria in the peri-infarct region of the cortex increased as result of EE training. Over 2 weeks, EE training significantly increased mitochondrial biogenesis-associated protein expression and mitochondrial function. A possible mechanism of the EE leading to the improvement of neurological function is that it increases brain mitochondrial biogenesis after the rats' cerebral ischaemia-reperfusion injury. Mitochondrial biogenesis stimulation or enhancement could become an innovative strategy for neuroprotection in future treatment.