Abstract: BACKGROUND: Patients with Alzheimer’s disease mainly show cognitive and memory dysfunctions. Aerobic exercise can inhibit endoplasmic reticulum stress and improve cognitive function of the patients. However, whether aerobic exercise can inhibit endoplasmic reticulum stress dependent neuroinflammation is still unclear.
OBJECTIVE: To explore the effect of aerobic exercise on neuroinflammation and cognitive impairment in a mouse model of Alzheimer’s disease. 
METHODS: Fifty C57BL/6J wild-type male mouse mice were randomly divided into wild-type control and wild-type exercise groups, while another 50 APP/PS1 double transgenic male mice were randomly divided into Alzheimer’s disease group and Alzheimer's disease exercise group, with 25 mice in each group. Mice in the wild-type exercise and Alzheimer's disease exercise groups received aerobic exercise training (treadmill training, 45 min/d, 12 m/min, 5 d/wk, 8 weeks in total). Mice in the wild-type control and Alzheimer’s disease groups were placed on the quiet running platform. Morris water maze test was used to detect the cognitive ability of mice. Hematoxylin-eosin staining and Nissl staining were used to detect hippocampal tissue damage in mice. Thioflavin-S staining was used to detect β-amyloid content in hippocampal tissue. Immunohistochemistry was used to detect β-amyloid and p-Tau levels in hippocampal tissue. Immunofluorescence staining was used to detect the number of positive cells for neuroinflammation-related factors in hippocampal tissue. Western blot was used to detect p-IRE1, IRE1, p-PERK, PERK, ATF6, GRP78, Bip, Caspase-12, Iba-1, and GFAP protein levels. 
RESULTS AND CONCLUSION: Compared with the wild-type control group, escape latency was increased, the number of times they reached the previous platform and the time they stayed on the platform were decreased, β-amyloid and Tau levels, p-IRE1/IRE1, p-PERK/PERK, ATF6, GRP78, Bip, Caspase-12, Iba-1, 
and GFAP protein levels, Iba-1+, Iba-1+TNF-α+, Iba-1+IL-6+, Iba-1+IL-1β+, GFAP+, GFAP+TNF-α+, GFAP+IL-6+, GFAP+IL-1β+ positive cells in hippocampal tissue were increased, and Iba-1+IL-4+, Iba-1+IL-10+, GFAP+IL-4+, GFAP+IL-10+ positive cells were decreased in the Alzheimer’s disease group (P < 0.05). Compared with Alzheimer’s disease group, escape latency was decreased, the number of times they reached the previous platform and the time they stayed on the platform were increased, β-amyloid and Tau levels, p-IRE1/IRE1, p-PERK/PERK, ATF6, GRP78, Bip, Caspase-12, Iba-1, GFAP protein levels, Iba-1+, Iba-1+TNF-α+, Iba-1+IL-6+, Iba-1+IL-1β+, GFAP+, GFAP+TNF-α+, GFAP+IL-6+, and GFAP+IL-1β+ positive cells in hippocampal tissue were decreased, and Iba-1+IL-4+, Iba-1+IL-10+, GFAP+IL-4+, GFAP+IL-10+ positive cells were increased in the Alzheimer’s disease exercise group (P < 0.05). To conclude, aerobic exercise can reduce cognitive impairment in Alzheimer’s disease mice by inhibiting endoplasmic reticulum stress and neuroinflammation in hippocampal tissue.

Key words: Alzheimer’s disease, aerobic exercise, endoplasmic reticulum stress, neuroinflammation, cognitive impairment