Physical exercise alters the activation of downstream proteins related to BDNF‐TrkB signaling in male Wistar rats with epilepsy

Abstract

There are a considerable number of studies concerning the behavioral effects of physical exercise on the epileptic brain; however, the intracellular signaling mechanisms involved remain unclear. We investigated the effects of aerobic exercise on hippocampal levels of brain-derived neurotrophic factor (BDNF), expression of its receptor tropomyosin receptor kinase B (TrkB), and activation of intracellular proteins related to BDNF-TrkB signaling in male Wistar rats with pilocarpine-induced epilepsy. Thirty days after the first spontaneous seizure, rats from the exercise group undertook a 30-day physical exercise program on the treadmill. Thereafter, BDNF levels, expression of TrkB, and activation of intracellular proteins were quantified by enzyme-linked immunosorbent assay, Western blotting, and multiplex assay, respectively. Statistical analyses were conducted using nonparametric tests. Rats with epilepsy presented decreased BDNF levels compared with control rats. BDNF levels increased significantly in the exercise group compared with the epileptic and control groups. Expression of full-length and truncated TrkB was increased in rats with epilepsy, and physical exercise restored its expression to control levels. RAC-alpha serine/threonine-protein kinase, mammalian target of rapamycin, and extracellular signal-regulated kinase activation were reduced in rats with epilepsy, and exercise increased activation compared with control and epilepsy groups. Increased cAMP response element binding protein activation was observed in the exercise group compared with the epilepsy group. Our findings indicate that the beneficial effects of exercise in the epileptic brain can be in part related to alterations in the activation of proteins related to the BDNF-TrkB signaling pathway.

Rb1, the Primary Active Ingredient in Panax ginseng C.A. Meyer, Exerts Antidepressant-Like Effects via the BDNF–Trkb–CREB Pathway

“…Collectively, our research indicates that Rb1 exerts antidepressant-like effects in a mouse model of CUMS-induced depression by promoting BDNF signaling, thus providing new insights into the pharmacological effects of Rb1 in the treatment of depression. In addition to depression, BDNF signaling is also involved in other neurological disorders such as anxiety and epilepsy (Bahi, 2017; De Almeida et al, 2017), suggesting that Rb1 may also be beneficial for treating these diseases; however, this requires further experimental evidence. Rb1 is increasingly recognized as an important neurotrophic factor, with potential for application in ameliorating central nervous system disorders.…”

The Contribution of Physical Exercise to Brain Resilience

“…Recently, we examined the influence of exercise on the activation of downstream proteins related to BDNF-TrkB receptor. Aerobic exercise increased hippocampal BDNF expression, restored the overexpression of full-length TrkB and truncated-TrkB isoforms to control levels, and altered the hippocampal activation of some proteins linked to BDNF-TrkB intracellular signaling (de Almeida et al, 2018) and resistance exercise restored to control levels the altered BDNF levels and ERK and mTOR activation in rats with epilepsy (de Almeida et al, 2017). Thus, improved learning and memory in rats with epilepsy housed in an enriched environment with wheel running was accompanied by increased hippocampal neurogenesis and BDNF and VEGF transcripts (Fares et al, 2013).…”

Exercise-linked consequences on epilepsy

“…Finally, it has been reported that physical exercise reduces the number of seizures in rats with epilepsy with [92] and without comorbidities [80,84]. Rats undergoing training prior to the application of pilocarpine are resistant to induction of status epilepticus, indicating the preventive effect of exercise on the development of epilepsy [93].…”

“…The release of BDNF can reverse not only cognitive decline but also decrease the number of seizures [78]. Epileptic rats submitted to exercise have BDNF values closer to normal [81,84].…”