Long-Term Moderate Exercise Rescues Age-Related Decline in Hippocampal Neuronal Complexity and Memory

Abstract

Background: Aging impairs hippocampal neuroplasticity and hippocampus-related learning and memory. In contrast, exercise training is known to improve hippocampal neuronal function. However, whether exercise is capable of restoring memory function in old animals is less clear. Objective: Here, we investigated the effects of exercise on the hippocampal neuroplasticity and memory functions during aging. Methods: Young (3 months), middle-aged (9–12 months), and old (18 months) mice underwent moderate-intensity treadmill running training for 6 weeks, and their hippocampus-related learning and memory, and the plasticity of their CA1 neurons was evaluated. Results: The memory performance (Morris water maze and novel object recognition tests), and dendritic complexity (branch and length) and spine density of their hippocampal CA1 neurons decreased as their age increased. The induction and maintenance of high-frequency stimulation-induced long-term potentiation in the CA1 area and the expressions of neuroplasticity-related proteins were not affected by age. Treadmill running increased CA1 neuron long-term potentiation and dendritic complexity in all three age groups, and it restored the learning and memory ability in middle-aged and old mice. Furthermore, treadmill running upregulated the hippocampal expressions of brain-derived neurotrophic factor and monocarboxylate transporter-4 in middle-aged mice, glutamine synthetase in old mice, and full-length TrkB in middle-aged and old mice. Conclusion: The hippocampus-related memory function declines from middle age, but long-term moderate-intensity running effectively increased hippocampal neuroplasticity and memory in mice of different ages, even when the memory impairment had progressed to an advanced stage. Thus, long-term, moderate intensity exercise training might be a way of delaying and treating aging-related memory decline.

DiI‐mediated analysis of presynaptic and postsynaptic structures in human postmortem brain tissue

“…Though this may seem surprising given the importance of hippocampal CA1 neurons to learning and memory, our results are consistent with studies from rodents and nonhuman primates. Studies consistently demonstrate that hippocampal dendritic trees, spine density, and excitatory synapse density undergoes little to no change during normal aging in mice, rats, and monkeys (Curcio & Hinds, ; Flood & Coleman, ; Gonzalez‐Ramirez, Velazquez‐Zamora, Olvera‐Cortes, & Gonzalez‐Burgos, ; Markham, McKian, Stroup, & Juraska, ; Morrison & Baxter, ; Pereira et al, ; Tsai et al, ). Although dendritic spines are relatively stable in CA1, aging may decrease the size of postsynaptic densities in CA1 (Morrison & Baxter, ).…”

Physical Exercise Inhibits Inflammation and Microglial Activation

“…These factors, amongst others, involve trophic effects, anti-oxidation, energy metabolism, and anti-inflammation. Some of these factors enhance brain function and ameliorate brain disorders by inducing neuroplasticity, increasing metabolic efficiency, and improving anti-oxidative capacity [1,2,3,4]. Others maintain brain homeostasis and protect brain from pathological insults by regulating glial activation and neuroinflammation.…”

Effects of Embryonic Inflammation and Adolescent Psychosocial Environment on Cognition and Hippocampal Staufen in Middle-Aged Mice

“…The hippocampus is an organ that is susceptible to the effects of aging, and plays an important role in spatial learning and memory (Moorthi et al, 2015;Tsai et al, 2018). There is growing evidence to suggest that hippocampal synaptic function and plasticity play a key role in age-associated learning and memory impairments (Mendelsohn and Larrick, 2012).…”