Exercise opens a temporal window for enhanced cognitive improvement from subsequent physical activity

Abstract

The beneficial effects of exercise on cognition are well established; however specific exercise parameters regarding the frequency and duration of physical activity that provide optimal cognitive health have not been well defined. Here, we explore the effects of the duration of exercise and sedentary periods on long-term object location memory (OLM) in mice. We use a weak object location training paradigm that is subthreshold for long-term memory formation in sedentary controls, and demonstrate that exercise enables long-term memories to form. We show that 14- and 21-d of running wheel access enables mice to discriminate between familiar and novel object locations after a 24 h delay, while 2- or 7-d running wheel access provides insufficient exercise for such memory enhancement using the subthreshold learning paradigm. After 14- and 21-d of wheel running, exercise-induced cognitive enhancement then decays back to baseline performance following 3-d of sedentary activity. However, exercise-induced cognitive enhancement can be reactivated by an additional period of just 2 d exercise, previously shown to be insufficient to induce cognitive enhancement on its own. The reactivating period of exercise is capable of enhancing memory after three- or seven-sedentary days, but not 14-d. These data suggest a type of “molecular memory” for the exercise stimulus, in that once exercise duration reaches a certain threshold, it establishes a temporal window during which subsequent low-level exercise can capitalize on the neurobiological adaptations induced by the initial period of exercise, enabling it to maintain the benefits on cognitive function. These findings provide new information that may help to guide future clinical studies in exercise.

Appropriate exercise level attenuates gut dysbiosis and valeric acid increase to improve neuroplasticity and cognitive function after surgery in mice

“…Exercise has been shown to improve learning and memory of animals modeled for various diseases [ 38 , 39 ]. However, the effects of exercise on control animals are not consistent: both beneficial and no effects on learning and memory have been reported [ 40 – 42 ]. Specifically, four studies that used Barnes maze and/or novel object recognition tests to assess learning and memory in control mice with or without exercise were identified.…”

Early life exercise primes the neural epigenome to facilitate gene expression and hippocampal memory consolidation

“…Identifying gene regulatory mechanisms activated by exercise during sensitive developmental periods can aid in understanding how early-life exercise may promote a "molecular memory" of exercise 23,60 , via the epigenome, that informs long-term cell Our study focuses on the impact of exercise on hippocampal gene expression and associated epigenetic modifications specifically during juvenile -adolescent periods (the fourth through sixth postnatal weeks of life in mice). We discover gene expression programs, and alterations in the histone modifications H4K8ac and H3K27me3, that may be unique to this early-life period.…”

“…This finding was associated with increased long-term potentiation (LTP) as well as modulations to synaptic physiology in hippocampal CA1 17 . Notably, the hippocampal memory effects of juvenile ELE during P21-27 persisted two weeks after exercise cessation, which is longer than the effect of exercise on adult hippocampal function 23 .…”

“…Although the majority of these studies have been performed in adults, more recent work suggests that the effects of exercise on hippocampal memory and the associated alterations in neurotrophic factor expression, synaptic plasticity, and neurogenesis are similar in juvenile and adolescent periods 17,[24][25][26][27] . Previous work in our lab showed that early-life exercise (ELE) for either one week (juvenile period; postnatal days (P) [21][22][23][24][25][26][27] or three weeks (juvenile-adolescence; P21-41) facilitated hippocampal long-term memory formation in response to a learning stimulus typically insufficient for forming long-term memory. This finding was associated with increased long-term potentiation (LTP) as well as modulations to synaptic physiology in hippocampal CA1 17 .…”

“…This suggests that exercise engages epigenetic regulatory mechanisms to promote plasticity. Adult exercise also opens a temporal window for persistent improvements to memory performance when a reactivating exercise exposure is introduced 23 . This suggests a "molecular memory" of the initial exercise 23 .…”