Running for REST: Physical activity attenuates neuroinflammation in the hippocampus of aged mice

•Aging increases REST mRNA in the hippocampus of 21-22 months-old mice.•Aging increases IL-1β and IL-10 mRNA in the hippocampus of aged mice.•Eight-weeks of physical activity attenuated sickness behavior of aged mice.•Physical activity increases BDNF and REST mRNA in the hippocampus of aged mice.•Physical activity decreases IL-1β and IL-10 mRNA in the hippocampus of aged mice.

Exercise improves mental health and synaptic function in the aged brain. However, the molecular mechanisms involved in exercise-induced healthy brain aging are not well understood. Evidence supports the role of neurogenesis and neurotrophins in exercise-induced neuroplasticity. The gene silencing transcription factor neuronal RE1-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) and an anti-inflammatory role of exercise are also candidate mechanisms. We evaluate the effect of 8 weeks of physical activity on running wheels (RW) on motor and depressive-like behavior and hippocampal gene expression of brain-derived neurotrophic factor (BDNF), REST, and interleukins IL-1β and IL-10 of adult and aged C57BL/6 mice. The aged animals exhibited impaired motor function and a depressive-like behavior: decreased mobility in the RW and open field and severe immobility in the tail suspension test. The gene expression of REST, IL-1β, and IL-10 was increased in the hippocampus of aged mice. Physical activity was anxiolytic and antidepressant and improved motor behavior in aged animals. Physical activity also boosted BDNF and REST expression and decreased IL-1β and IL-10 expression in the hippocampus of aged animals. These results support the beneficial role of REST in the aged brain, which can be further enhanced by regular physical activity.