Hindlimb Unloading Induces Apoptosis and Autophagy but Not Neurodegeneration in the Hippocampus of the Rats

Physical activity is well known to have a beneficial effect on whole body functions, whereas a sedentary lifestyle contributes to the development of metabolic and other diseases and can lead to cognitive decline and increased risk of dementia. The hippocampus mainly controls cognitive performance and the hippocampal neurodegeneration is directly correlated with dementia progression. Hindlimb unloading (HU) is a widely used method to simulate microgravity in rodents and can be used as a model of mobility restriction since one of the main factors of HU is muscle disuse. Additionally, rodents show impaired learning and memory after long-term HU. Here, we explored whether HU would affect the survival or death of the hippocampal cells. Our data demonstrated that after 3-day HU, both apoptosis and autophagy were activated in the hippocampus, as evidenced by the activation of caspase 3 and 9 and an increase in the number of Cathepsin D and LC3b double-positive cells correspondently. Our data indicated that HU has no deleterious effects leading to neurodegeneration for up to 14 days. Moreover, our results also showed that the activation of autophagy during short-term HU had a protective effect, as we did not observe any cell loss or damage.