Dramatic impacts on brain pathology, anxiety, and cognitive function in the knock-in APPNL-G-F mouse model of Alzheimer disease following long-term voluntary exercise

Abstract

Background An active lifestyle is associated with improved cognitive functions in aged people and may prevent or slow down the progression of various neurodegenerative diseases including Alzheimer’s disease (AD). To investigate these protective effects, male APPNL-G-F mice were exposed to long-term voluntary exercise. Methods Three-month-old AD mice were housed in a cage supplemented with a running wheel for 9 months for long-term exercise. At the age of 12 months, behavioral tests were completed for all groups. After completing behavioral testing, their brains were assessed for amyloid pathology, microgliosis, and cholinergic cells. Results The results showed that APPNL-G-F mice allowed to voluntarily exercise showed an improvement in cognitive functions. Furthermore, long-term exercise also improved anxiety in APPNL-G-F mice as assessed by measuring thigmotaxis in the Morris water task. We also found reductions in amyloid load and microgliosis, and a preservation of cholinergic cells in the brain of APPNL-G-F mice allowed to exercise in their home cages. These profound reductions in brain pathology associated with AD are likely responsible for the observed improvement of learning and memory functions following extensive and regular exercise. Conclusion These findings suggest the potential of physical exercise to mitigate the cognitive deficits in AD.

Development and validation of prechiasmatic mouse model of subarachnoid hemorrhage to measure long-term neurobehavioral impairment

“…Statistical analysis was performed using GraphPad Prism 9.0 (GraphPad Software Inc., CA, USA). We estimated sample sizes using effect sizes based on our previous publications [27][28][29]31] and pilot experiments. The sample size for the twosample t-test was four to ve per group.…”

“…The Y-maze test is a method used to evaluate spatial working and reference memory in rodents, as described in previous studies [27][28][29]. Brie y, The test involves a Y-shaped maze consisting of three white, opaque plastic arms at a 120° angle.…”

“…The NOR test is a widely used method for assessing the memory of rodents. The test is based on the innate inquisitiveness of rodents to explore novel objects and retain their spatial memory [28][29][30][31]. The test was conducted in an open-eld arena, to which the mice were rst habituated.…”

“…FC test was conducted to evaluate amygdala-and hippocampus-dependent memory in rodents, as described in our previous publications [27,29,31]. The test was carried out in an acrylic square chamber (33 × 33 × 25 cm) with a stainless steel rod oor that was connected to a shock generator for delivering a footshock.…”

“…Immunohistochemistry was performed as previously described [6, 8, [27][28][29]32]. Free-oating brain sections with a thickness of 40-µm were subjected to uorescent immunohistochemical staining using the following primary antibodies: anti-mouse brinogen (ab34269, 1:1000 dilution), anti-Iba1 monoclonal antibody (MA5-27726, 1:1000 dilution), anti-P2RY12 monoclonal antibody (MABN2593, 1:1000 dilution), and anti-glial acidic brillary protein (GFAP) (IF03L, 1:1000 dilution).…”