Effects of Aerobic Exercise Training on Mitochondrial Ca2+ Homeostasis and Apoptosis in the Hippocampus of Type 2 Diabetic Rats

Abstract

Abstracts PURPOSE Type 2 diabetes mellitus (T2DM) is a recognized risk factor for neurodegenerative diseases such as Alzheimer's disease (AD). Mitochondrial dysfunction caused by disturbance of calcium (Ca2+) homeostasis might be a pathophysiological link between T2DM and AD. In the present study, we investigated the effects of aerobic training on the regulation of mitochondrial calcium homeo-stasis, mitochondrial function (O2 respiration), and apoptosis in the hippocampus of T2DM rats. METHODS Thirty male Otsuka Long-Evans Tokushima Fatty rats were divided into three groups: control group (CON, n=10), diabetes control group (DM, n=10), and diabetes+aerobic exercise group (DM+EXE, n=10). The rats in the exercise group were forced to run on a treadmill for 30 min, three times a week for 8 weeks. RESULTS The DM group showed significantly increased mitochondrial calcium uniporter (MCU) protein and apoptosis-related factors such as Bax and caspase-3 and decreased mitochondrial O2 respiration when compared with the CON group. However, the hippocampus of rats in the DM+EXE group exhibited a significant decrease in MCU, Bax, and caspase-3 levels and an increase in Bcl-2 and mitochondrial O2 respiration when compared with the DM group. CONCLUSIONS These results suggest that regular aerobic exercise alleviates mitochondrial dysfunction and apoptosis by modulating MCU, which is involved in mitochondrial Ca2+ homeostasis in the early stages of T2DM. This might be a potent strategy to prevent neurodegenerative diseases.

Keywords

• type 2 diabetes
• neurodegenerative diseases
• mitochondrial calcium homeostasis
• exercise