Aerobic exercise has been experimentally proved to improve the blood supply of the brain after brain injury. In clinical practice, aerobic exercise is effective in treating Alzheimer’s disease, but the research on its mechanism is still at a blank stage.
To explore the mechanism by which aerobic exercise protects the brain of amyloid β-protein (Aβ) 1-42-induced dementia rats through the adenosine monophosphate activated protein kinase (AMPK)/endothelial nitric oxide synthase (eNOS)/nuclear factor κB (NF-κB) signaling pathway.
A total of 80 SPF Sprague-Dawley male rats were randomly divided into 4 groups (n=20 per group): sham operation group, model group, aerobic exercise group, and inhibitor group. Animal model of Aβ1-42-induced Alzheimer’s disease was made in each rat except for the sham operation group. In the sham operation group, 2 μL of normal saline was injected after cutting the dura mater. On the 3rd day after modeling, the inhibitor group was intraperitoneally injected with 2 mL of 50 mg/L AMPK Compound C, and the other groups were injected with the same amount of normal saline. After the injection, the rats in the aerobic exercise group and inhibitor group received 12 weeks of aerobic exercise training, and those in the sham operation group and model group received no treatment. After exercise, the changes in the spatial learning and memory ability of the rats were detected by water maze test and step down test; laser speckle imaging, hematoxylin-eosin staining, ELISA, and immunofluorescence were used to detect the changes in cerebral cortex blood flow, cerebral infarction volume, neuronal damage in brain tissue, expression levels of interleukin 1β, interleukin 6, and tumor necrosis factor α in brain tissue, nuclear translocation of NF-κB; western blot assay was used to detect the expression levels of p-AMPK, p-eNOS and NF-κB proteins.
RESULTS AND CONCLUSION:
Compared with the sham operation group, the rats in the model group had significantly prolonged escape latency, reduced number of times passing through the original quadrant where the original platform was located, reduced blood perfusion volume in the cerebral cortex, increased expression levels of interleukin 6 and tumor necrosis factor α, enhanced fluorescence intensity of nuclear translocation of NF-κB in brain tissue, reduced expression levels of p-AMPK and p-eNOS in brain tissue, and increased expression of NF-κB protein (all P < 0.05). Compared with the model group, in the aerobic exercise group, the escape latency was significantly decreased, the number of times passing through the quadrant where the original platform was located was significantly increased, the cerebral cortex blood perfusion was significantly increased, the apoptosis rate in the brain tissue and expression levels of interleukin 1β, interleukin 6 and tumor necrosis factor α decreased, the fluorescence intensity of NF-κB nuclear translocation in the brain tissue was significantly weakened, and the expression levels of p-AMPK and p-eNOS in the brain tissue were significantly increased, and NF-κB protein expression was significantly decreased (all P < 0.05). Compared with the aerobic exercise group, the above indicators in the inhibitor group were significantly reversed (P < 0.05). To conclude, aerobic exercise may inhibit the activation of NF-κB by activating AMPK/eNOS/NF-κB signals, and thereby reduce inflammatory response, which plays a protective effect against Aβ1-42 induced senile dementia.