Physical training in developing rats does not influence the kindling development in the adult life

Abstract

The positive effect of physical exercise programs on seizure frequency and severity has been demonstrated both in adult human and animals. However, this investigation during animal brain development has not been examined. To this purpose, the present work was aimed to analyse the effect of physical exercise training in rats after weaning on the kindling process in the adulthood. Thirty rats were divided into 3 groups: the first group (EX = 10) was submitted to daily bout of aerobic exercise (60 min running on the treadmill at 24/26 m/min) between P21 and 60 days of age. After this period of training, animals were submitted to 60 min running at the same speed and kindling stimulated one min post-exercise. The second group (SHAM = 10) was maintained in the treadmill for the same time as the trained group without being submitted to physical exercise. The third group served as control (CTL = 10). The number of stimulations required to reach stage 5 for the EX group was not statistically different from CTL and SHAM groups. However, the EX group spent a longer time and a shorter afterdischarge (AD) in stage 1 compared to the CTL and SHAM groups. The number of stimulations and AD duration in stage 2, 3 and 4 was not statistically different between all the groups. Taken together, our study showed that although forced physical exercise in developing rats does not exert significant influence to reach the stage 5 of amygdala kindling in the adult life its interference during the process of epileptogenesis indicate a positive effect of exercise in developing brain.

Introduction

Several investigations on the relationship of physical exercise and epilepsy have been carried out. Clinically, it has been demonstrated that there is a reduction in the number of seizures after physical exercise or physical training programs [1], [2], although the mechanisms underlying this protective effect have not been clearly investigated [1], [3]. However, experiments on brain electrical activity have shown that abnormal discharges could decrease or even disappear in patients during physical activity that eventually could return at rest [4], [5]. Other researches have suggested that physical exercise might raise the seizure threshold and, consequently, could confer a protective effect on people with epilepsy [4], [6]. On the other hand, there is little evidence of seizure-induced by physical exercise. Most of previously reported cases had a history of additional seizures independent of exercise [7], [8], [9].

In our laboratory we have been investigating the effect of physical exercise in some experimental models of epilepsy [10], [11]. Accordingly, we observed that in rats, physical training, performed before and during the kindling procedure, retarded the amygdala kindling development [10]. In addition, we reported that aerobic physical program reduced the frequency of spontaneous recurrent seizures in the pilocarpine model of epilepsy in rats [11]. Metabolic [12] and electrophysiological [13] studies have also been performed to understand these positive effects of exercise on epilepsy.

Besides physical training programs, other strategies have been used to study neuroplastic changes that occur in consequence of a brain insult. For instance, exposing animals to more complex environments has been shown to attenuate or reverse the sequelae of central nervous system insults such as seizures, ischemia, infarct, cortical lesion, and traumatic brain injury [14], [15], [16], [17], [18]. However, most of the works mentioned above deal with adult animals with only few studies dedicated to investigate the relation of physical activity with the epileptic phenomenon in developing animals. One of these studies was conducted by Faverjon and co-workers [19] who showed that environmental enrichment can considerably improve the performance in the water maze of adolescent rats subjected to status epilepticus at the time of weaning. This improvement in cognitive function was associated with increases in neurogenesis in the granule cell layer of the dentate gyrus and activation of phosphorylated cyclic adenosine 3′:5′-cyclic phosphatase (cAMP) response element binding protein (pCREB), a transcription factor that plays a critical role in memory.

As mentioned above, we have observed that a program of physical exercise inhibits amygdala kindling development in adult rats [10], and considering the possible mechanisms that could underlie neuronal and plastic changes occurring during both physical training and brain development, the aim of this work was to examine whether physical activity performed during the animal development could modify epileptogenesis in the long-run. To this purpose, we analysed in rats the effect of a post-weaning physical exercise program on amygdala kindling during the adulthood.