Effects of involuntary treadmill running in combination with swimming on adult neurogenesis in an Alzheimer's mouse model

Physical exercise plays a role on the prevention and treatment of Alzheimer's disease (AD), but the exercise mode and the mechanism for these positive effects is still ambiguous. Here, we investigated the effect of an aerobic interval exercise, running in combination with swimming, on behavioral dysfunction and associated adult neurogenesis in a mouse model of AD. We demonstrate that 4 weeks of the exercise could ameliorate Aβ₄₂ oligomer-induced cognitive impairment in mice utilizing Morris water maze tests. Additionally, the exercised Aβ₄₂ oligomer-induced mice exhibited a significant reduction of anxiety- and depression-like behaviors compared to the sedentary Aβ₄₂ oligomer-induced mice utilizing an Elevated zero maze and a Tail suspension test. Moreover, by utilizing 5'-bromodeoxyuridine (BrdU) as an exogenous cell tracer, we found that the exercised Aβ₄₂ oligomer-induced mice displayed a significant increase in newborn cells (BrdU⁺ cells), which differentiated into a majority of neurons (BrdU⁺ DCX⁺ cells or BrdU⁺NeuN⁺ cells) and a few of astrocytes (BrdU⁺GFAP⁺ cells). Likewise, the exercised Aβ₄₂ oligomer-induced mice also displayed the higher levels of NeuN, PSD95, synaptophysin, Bcl-2 and lower level of GFAP protein. Furthermore, alteration of serum metabolites in transgenic AD mice between the exercised and sedentary group were significantly associated with lipid metabolism, amino acid metabolism, and neurotransmitters. These findings suggest that combined aerobic interval exercise-mediated metabolites and proteins contributed to improving adult neurogenesis and behavioral performance after AD pathology, which might provide a promising therapeutic strategy for AD.