Exercise-induced plasticity of AMPA-type glutamate receptor subunits in the rat brain

Abstract

The aim of this study was to analyze the plastic effects of moderate exercise upon the motor cortex (M1 and M2 areas), cerebellum (Cb), and striatum (CPu) of the rat brain. This assessment was made by verifying the expression of AMPA-type glutamate receptor subunits (GluR1 and GluR2/3). We used adult Wistar rats, divided into 5 groups based on duration of exercise training, namely 3 days (EX3), 7 days (EX7), 15 days (EX15), 30 days (EX30), and sedentary (S). The exercised animals were subjected to a treadmill exercise protocol at the speed of the 10 meters/min for 40 min. After exercise, the brains were subjected to immunohistochemistry and immunoblotting to analyze changes of GluR1 and GluR2/3, and plasma corticosterone was measured by ELISA in order to verify potential stress induced by physical training. Overall, the results of immunohistochemistry and immunoblotting were similar and revealed that GluR subunits show distinct responses over the exercise periods and for the different structures analyzed. In general, there was increased expression of GluR subunits after longer exercise periods (such as EX30), although some opposite effects were seen after short periods of exercise (EX3). In a few cases, biphasic patterns with decreases and subsequent increases of GluR expression were seen and may represent the outcome of exercise-dependent, complex regulatory processes. The data show that the protocol used was able to promote plastic GluR changes during exercise, suggesting a specific involvement of these receptors in exercise-induced plasticity processes in the brain areas tested.

Exercise attenuates levodopa-induced dyskinesia in 6-hydroxydopamine-lesioned mice

“…This would be a tight analogy with the ability of exercise to attenuate memory impairment in Parkinsonism (Aguiar et al, 2009), which involves a growth factor mediated (reviewed in Cotman and Berchtold, 2002). An alternative hypothesis would be an impact of exercise on the glutamatergic afferents driving the basal ganglia, in accordance with the impact of exercise on the morpho-functional plasticity of glutamatergic synapses (Real et al, 2010, VanLeeuwen et al, 2010 that are known to be affected in dyskinetic animals (Kobylecki et al, 2010, Sgambato-Faure andCenci, 2012).…”

Exercise alters resting-state functional connectivity of motor circuits in parkinsonian rats

“…Consistent with these human findings of neuroplasticity, rat models have suggested exercise-dependent synaptogenesis. Here treadmill training results in an increase in the expression of AMPA receptor subunit, synapsin I, and synaptophysin in the motor cortices (Garcia, et al, 2012, Real, et al, 2010), as well as in an increase in synaptophysin expression in the ventromedial thalamic nucleus (Ding, et al, 2002). …”

“…In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonian mice treadmill running similarly increases D 2 receptor binding (Vuckovic, et al, 2010) and reverses dendritic spine loss (Toy, et al, 2014) in the dorsolateral striatum. Treadmill exercise in rats has also been shown to increase the expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor subunits, synapsin I, synaptophysin, and neurofilaments in the striatum (Garcia, et al, 2012, Real, et al, 2010). Such exercise-induced neuroplasticity may contribute to the reintegration of dlCPu and increased functional connectivity of aCPu and vlCPu.…”

Neuroplasticidade induzida pelo exercício: efeitos sobre o hipocampo e regiões motoras do encéfalo de ratos.

“…Os animais foram treinados em uma esteira ergométrica programável (KT 3000 -IMBRAMED) adaptada para ratos ( Fig.2-6 (Felix e Michelini, 2007), sendo o primeiro minuto a 0,4 km/h, o segundo minuto a 0,5 km/h e os demais minutos a 0,6 km/h (10m/min) Real et al, 2010). Com o intuito de minimizar o estresse dos animais, optamos por não realizar teste de esforço e considerar os valores de VO 2 máximo já obtidos em outros projetos do nosso departamento (Felix e Michelini, 2007 Figura 2-6.…”

“…Foi demostrado que o exercício voluntário e o exercício forçado podem ativar vias de sinalização distintas (Chen et al, 2007), o que pode explicar diferenças entre alguns relatos da literatura e nossos achados. Preocupamos-nos em minimizar fatores estressantes, excluindo a fase de teste de esforço do protocolo, iniciando os procedimentos por uma fase de adaptação à esteira, onde o animal tem os primeiros contatos com o equipamento, e utilizando uma velocidade de treinamento moderada (0,6 km/h) Real et al, 2010), uma vez que foram observados altos níveis de cortisol em ratos submetidos a treinamento monitorado e com velocidades mais altas . Um protocolo de corrida estressante (1h a 25m/min) e familiarização insuficiente dos ratos à esteira e ao ambiente onde serão realizados os exercícios podem resultar em ratos altamente estressados como indicado pelo aumento da resposta da amígdala (Timofeeva et al,71 2003; Vissing et al, 1996).…”