Exercise-induced upregulation of TRIM9 attenuates neuroinflammation in Alzheimer's disease-like rat

Abstract

Objective: Exercise exerts protective effects against Alzheimer's disease (AD). However, the factors and mechanisms underlying these effects remain largely unknown. This study aims to elucidate the molecular mechanisms by which exercise exerts its protective effects against AD.

Methods: Male 7-week-old Sprague-Dawley rats were randomly allocated to four groups (n = 10 per group): control (CON), exercise control (EXE), sedentary AD model induced by intracerebroventricular streptozotocin (STZ) injection, and AD model with treadmill exercise (EXE + STZ). The exercise groups underwent a 13-week treadmill exercise. An intracerebroventricular injection of STZ was used to induce a rat model of AD. The Barnes maze task was employed as an assessment of spatial learning and memory. Hippocampal tissues from three rats per group was collected for proteomic analysis. Immunofluorescence staining, western blot analysis and polymerase chain reaction were performed for the evaluation of Aβ production, tau hyperphosphorylation, differential protein and corresponding signaling pathway.

Results: Treadmill exercise could significantly improve STZ-induced cognitive dysfunction and provide neuroprotection by reducing Aβ deposition and tau hyperphosphorylation. Proteomic analysis and further studies demonstrated that treadmill training could significantly increase the expression of tripartite motif-containing 9 (TRIM9). Subsequent research indicated that the upregulation of TRIM9 maybe due, in part,to the inhibition of the NF-κB pathway, thereby reducing the pro-inflammatory factor, and exerting an anti-inflammatory effect.

Conclusions: Treadmill exercise attenuates cognitive decline in AD models by upregulating TRIM9 expression, which in turn inhibits NF-κB-mediated neuroinflammation. These findings suggest that TRIM9 may serve as a potential therapeutic target for immunomodulatory strategies against AD.

Keywords: Aerobic exercise; Alzheimer’s disease; Neuroinflammation; Proteomics; Tripartite motif containing.