A single bout of exercise increases hippocampalBdnf: influence of chronic exercise and noradrenaline

Abstract

Research in human subjects suggests that acute exercise can improve memory performance, but the qualities of the exercise necessary to promote improved memory, and the signaling pathways that mediate these effects are unknown. Brain-derived neurotrophic factor (Bdnf), noradrenergic signaling, and post-translational modifications to AMPA receptors have all been implicated in the enhancement of memory following emotional or physical arousal; however, it is not known if a single bout of exercise is sufficient to engage these pathways. Here we use a rodent model to investigate the effects of acute and chronic exercise on hippocampal transcript-specific Bdnf expression and phosphorylation of the GluR1 subunit of the AMPA-type glutamate receptor. A single bout of treadmill exercise was insufficient to mimic the increased expression of GluR1 protein and phosphorylation at Ser845 observed following one month of voluntary wheel running. However, acute exercise was sufficient to increase Bdnf transcript IV mRNA expression in sedentary subjects, but not subjects housed for one month with a running wheel. High-intensity acute exercise increased total Bdnf mRNA in sedentary mice, but not above levels observed following chronic access to the running wheel. Although depletion of central noradrenergic signaling with DSP-4 reduced total Bdnf and Bdnf IV mRNA, the effect of acute exercise on Bdnf mRNA persisted. Our characterization of the effects of acute exercise on Bdnf expression and persistence in the absence of noradrenergic modulation may inform strategies to employ physical activity to combat cognitive aging and mental health disorders.

Acute forced exercise increasesBdnf IV mRNAand reduces exploratory behavior in C57BL/6J mice

“…We have previously shown that continuous exposure to a voluntary running wheel for one month resulted in an increase in the expression of GluR1 and phosphorylation of Ser845 . However, we observed no change in Ser845 phosphorylation 15 minutes after a single 45‐minute bout of treadmill exercise . Hu et al found elevated Ser845 phosphorylation 15 minutes following a peripheral injection of epinephrine, suggesting that the phosphorylation of Ser845 is induced rapidly.…”

“…Similarly, stimulation that reduces synaptic strength is associated with a rapid dephosphorylation of Ser845 . We have previously shown that continuous exposure to a voluntary running wheel for one month resulted in an increase in the expression of GluR1 and phosphorylation of Ser845 . However, we observed no change in Ser845 phosphorylation 15 minutes after a single 45‐minute bout of treadmill exercise .…”

“…BDNF transcript IV ( Bdnf IV ) is of particular interest, as it appears to be uniquely sensitive to neuronal stimuli in vitro and in vivo . We previously showed an increase in total Bdnf and Bdnf IV mRNA expression 15 minutes following a 45‐minute bout of treadmill exercise—an effect that was independent of exercise intensity. The exercise protocol utilized in our previous investigation was long (45 minutes) and employed a rest period (15 minutes) prior to determination of Bdnf expression, so the threshold of exercise duration and intensity is yet to be determined.…”

BDNF Integrity in Ageing and Stress

“…4 Lower serum levels are linked to greater symptom, cognitive, impairment. 5 Thus, interventions, as for example physical exercise, whether acute or chronic, endurance or resistance, promote the mobilization of BDNF and other neurotrophic factors 6,7 In the laboratory environment, several experimental models have been shown to accelerate the ageing process through disruptions in the normal functioning and integrity of BDNF. Social isolation/ deprivation of rats and mice induces chronic stress and may be applied usefully as a laboratory animal model for neuropsychiatric disorders, such as schizophrenia spectrum disorders and clinical depression.…”

Excessive Treadmill Training Enhances Brain-Specific MicroRNA-34a in the Mouse Hippocampus

“…Importantly, BDNF is a candidate mechanism underlying these exercise-induced benefits that help optimize brain plasticity outcomes via exercise intervention (Baptista and Andrade, 2018;Cooper et al, 2018). Acute high-intensity exercise increases the expression of BDNF (Venezia et al, 2017). Furthermore, MicroRNAs (miRNAs), small non-coding regulatory RNAs, are important regulators of various cellular processes via several signaling pathways relevant to exercise adaptation (Domańska-Senderowska et al, 2019).…”