Resistance Exercise Reduces Seizure Occurrence, Attenuates Memory Deficits and Restores BDNF Signaling in Rats with Chronic Epilepsy
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Epilepsy is a disease characterized by recurrent, unprovoked seizures. Cognitive impairment is an important comorbidity of chronic epilepsy. Human and animal model studies of epilepsy have shown that aerobic exercise induces beneficial structural and functional changes and reduces the number of seizures. However, little is yet understood about the effects of resistance exercise on epilepsy. We evaluated the effects of a resistance exercise program on the number of seizures, long-term memory and expression/activation of signaling proteins in rats with epilepsy. The number of seizures was quantified by video-monitoring and long-term memory was assessed by an inhibitory avoidance test. Using western blotting, multiplex and enzyme-linked immunosorbent assays, we determined the effects of a 4-week resistance exercise program on IGF-1 and BDNF levels and ERK, CREB, mTOR activation in the hippocampus of rats with epilepsy. Rats with epilepsy submitted to resistance exercise showed a decrease in the number of seizures compared to non-exercised epileptic rats. Memory deficits were attenuated by resistance exercise. Rats with epilepsy showed an increase in IGF-1 levels which were restored to control levels by resistance exercise. BDNF levels and ERK and mTOR activation were decreased in rats with epilepsy and resistance exercise restored these to control levels. In conclusion, resistance exercise reduced seizure occurrence and mitigated memory deficits in rats with epilepsy. These resistance exercise-induced beneficial effects can be related to changes in IGF-1 and BDNF levels and its signaling protein activation. Our findings indicate that the resistance exercise might be included as complementary therapeutic strategy for epilepsy treatment.
KeywordsEpilepsy Seizures Resistance exercise Long-term memory IGF-1 BDNF
This research study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; #300605/2013-07); Fundacão de Amparo à Pesquisa do Estado de São Paulo/ Programa Núcleos de Excelência (FAPESP/PRONEX; #14/00035-1; #2013/12692-4; #2011/50680-2).
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflicts of interest. All authors read and approved the final manuscript.
- 1.Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, Engel J Jr, Forsgren L, French JA, Glynn M, Hesdorffer DC, Lee BI, Mathern GW, Moshe SL, Perucca E, Scheffer IE, Tomson T, Watanabe M, Wiebe S (2014) ILAE official report: a practical clinical definition of epilepsy. Epilepsia 55(4):475–482CrossRefPubMedGoogle Scholar
- 13.Arida RM, Scorza CA, Scorza FA, Gomes da Silva S, da Graca Naffah-Mazzacoratti M, Cavalheiro EA (2007) Effects of different types of physical exercise on the staining of parvalbumin-positive neurons in the hippocampal formation of rats with epilepsy. Prog Neuropsychopharmacol Biol Psychiatry 31(4):814–822CrossRefPubMedGoogle Scholar
- 15.Sartori CR, Pelágio FC, Teixeira SA, Valentinuzzi VS, Nascimento AL, Rogério F, Muscará MN, Ferrari EA, Langone F (2009) Effects of voluntary running on spatial memory and mature brain-derived neurotrophic factor expression in mice hippocampus after status epilepticus. Behav Brain Res 203(2):165–172CrossRefPubMedGoogle Scholar
- 24.Tsai CL, Wang CH, Pan CY, Chen FC (2015) The effects of long-term resistance exercise on the relationship between neurocognitive performance and GH, IGF-1, and homocysteine levels in the elderly. Front. Behav Neurosci 9:23Google Scholar
- 29.Novaes Gomes FG, Fernandes J, Vannucci Campos D, Cassilhas RC, Viana GM, D’Almeida V, de Moraes Rego MK, Buainain PI, Cavalheiro EA, Arida RM (2014) The beneficial effects of strength exercise on hippocampal cell proliferation and apoptotic signaling is impaired by anabolic androgenic steroids. Psychoneuroendocrinology 50:106–117CrossRefPubMedGoogle Scholar
- 40.Zheng WH, Kar S, Quirion R (2002) Insulin-like growth factor-1-induced phosphorylation of transcription factor FKHRL1 is mediated by phosphatidylinositol 3-kinase/Akt kinase and role of this pathway in insulin-like growth factor-1-induced survival of cultured hippocampal neurons. Mol Pharmacol 62(2):225–233CrossRefPubMedGoogle Scholar
- 57.Field A (2009) Testes não paramétricos. In: Descobrindo a estatística usando o SPSS, 2ª edn. Artmed, Porto Alegre, pp 474–513Google Scholar
- 62.Walz R, Roesler R, Quevedo J, Rockenbach IC, Amaral OB, Vianna MR, Lenz G, Medina JH, Izquierdo I (1999) Dose-dependent impairment of inhibitory avoidance retention in rats by immediate post-training infusion of a mitogen-activated protein kinase kinase inhibitor into cortical structures. Behav Brain Res 105(2):219–223CrossRefPubMedGoogle Scholar