The weekend warrior effect: Consistent intermittent exercise induces persistent cognitive benefits.

Exercise provides a range of cognitive benefits, including improved memory performance. Previously, we demonstrated that 14 days of continuous voluntary wheel-running exercise enables learning in a hippocampus-dependent Object Location Memory (OLM) task under insufficient, subthreshold training conditions in adult mice. Whether similar exercise benefits can be obtained from consistent intermittent exercise as continuous exercise is unknown. Here, we examine whether intermittent exercise (the weekend warrior effect: 2 days of exercise a week for 7 weeks) displays similar or distinct cognitive benefits as previously examined with 14 days of continuous exercise. We find that both continuous and intermittent exercise parameters similarly enable hippocampus-dependent OLM compared to the 2-day exercise control group. Mice receiving intermittent exercise maintained cognitive benefits following a 7-day sedentary delay, whereas mice that underwent 14 continuous days of exercise showed diminished cognitive benefits as previously reported. Further, compared to continuous exercise, intermittent exercise mice exhibited persistently elevated levels of the genes Acvr1c and Bdnf which we know to be critically involved in hippocampus-dependent long-term memory in the dorsal hippocampus. Together findings suggest that consistent intermittent exercise persistently enables hippocampal-dependent long-term memory. Understanding the optimal parameters for persistent cognitive function and the mechanisms mediating persistent effects will aid in therapeutic pursuits investigating the mitigation of cognitive ailments.

Specific exercise patterns generate an epigenetic molecular memory window that drives long-term memory formation and identifies ACVR1C as a bidirectional regulator of memory in mice.

Exercise has beneficial effects on cognition throughout the lifespan. Here, we demonstrate that specific exercise patterns transform insufficient, subthreshold training into long-term memory in mice. Our findings reveal a potential molecular memory window such that subthreshold training within this window enables long-term memory formation. We performed RNA-seq on dorsal hippocampus and identify genes whose expression correlate with conditions in which exercise enables long-term memory formation. Among these genes we found Acvr1c, a member of the TGF ß family. We find that exercise, in any amount, alleviates epigenetic repression at the Acvr1c promoter during consolidation. Additionally, we find that ACVR1C can bidirectionally regulate synaptic plasticity and long-term memory in mice. Furthermore, Acvr1c expression is impaired in the aging human and mouse brain, as well as in the 5xFAD mouse model, and over-expression of Acvr1c enables learning and facilitates plasticity in mice. These data suggest that promoting ACVR1C may protect against cognitive impairment.