Simple and Complex Wheel Running Effect on Depression, Memory, Neuroinflammation, and Neurogenesis in Alzheimer's Rat Model

Introduction The aim of this study was to investigate 12 wk of simple and complex voluntary wheel running on Alzheimer's disease (AD), associated biomarkers, and behaviors. Methods Sixty male Wistar rats were randomly divided into six groups: healthy control (Con-Sed), AD only (AD-Sed), simple wheel control (SWC), complex wheel control (CWC), simple wheel AD (SWAD), and complex wheel AD (CWAD). Novelty-suppressed feeding test and the Morris water maze test were used to evaluate depression and memory, respectively. Ki67 was measured in the hippocampus, whereas interleukin (IL)-1β and neural/glial antigen 2 (NG2) were measured in both the hippocampus and the prefrontal cortex. One-way ANOVA with Tukey's post hoc test was performed. Results AD-Sed group had significantly lower spacial memory (P < 0.001) compared with Con-Sed. Simple and complex wheel running attenuated these deficits in the SWAD and CWAD groups, respectively (P < 0.001). Only the CWAD group had significantly improved novelty-suppressed feeding test time compared with AD-Sed (P < 0.001), equivalent to the healthy wheel running groups. AD-Sed has significantly higher hippocampal concentrations of Ki67 (P = 0.01) compared with the Con-Sed. Both SWAD and CWAD had significantly reduced Ki67 with similar concentrations compared with the SWC and CWC groups (P > 0.05). AD-Sed animals also presented with significantly higher hippocampal and prefrontal cortex concentrations of IL-1β compared with Con-Sed (P < 0.001). SWAD and CWAD had no effect in changing these concentrations. Complex wheel running significantly increased NG2 in the healthy control and AD models, whereas simple wheel running significantly increased NG2 in the AD model. Conclusions The results of our study suggest that complex wheel running might be more advantageous in promoting memory and neuroplasticity while reducing depression that is associated with AD.