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

• Published in: Journal of neuroscience research 2018-05, Vol.96 (5), p.911-920
• Main Authors: de Almeida, Alexandre Aparecido, Gomes da Silva, Sérgio, Lopim, Glauber Menezes, Vannucci Campos, Diego, Fernandes, Jansen, Cabral, Francisco Romero, Arida, Ricardo Mario
• Format: Article
• Language: English
• Subjects: Activation; Animals; BDNF; Brain; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; cell signaling; Epilepsy; Epilepsy - chemically induced; Epilepsy - metabolism; Exercise; Hippocampus; Hippocampus - metabolism; Intracellular; Intracellular signalling; Kinases; Male; Physical Conditioning, Animal - physiology; Physical exercise; Pilocarpine; Protein kinase; Proteins; Rapamycin; Rats; Rats, Wistar; Receptor, trkB - metabolism; Rodents; Seizures; Seizures - metabolism; Signal Transduction; Statistical analysis; Threonine; TOR protein; TrkB receptors; Tropomyosin; Western blotting
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.24196

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. Beneficial effects of physical exercise on epilepsy have been reported in the literature. In this study, we investigated one of the possible mechanisms by which physical exercise reduces seizure frequency in animals with epilepsy. An aerobic exercise program increased hippocampal BDNF levels, restored to control levels the overexpression of fl‐TrkB and tr‐TrkB isoforms and altered the hippocampal activation of some proteins linked to BDNF‐TrkB intracellular signaling. These present results strengthen the beneficial role of physical exercise as a complementary therapy for epilepsy.