Personalized Medicine Using Cutting Edge Technologies for Genetic Epilepsies.

Epilepsy is the most common chronic neurologic disorder in the world, affecting 1-2% of the population. Besides, 30% of epilepsy patients are drug-resistant. Genomic mutations seem to play a key role in its etiology and knowledge of strong effect mutations in protein structures might improve prediction and the development of efficacious drugs to treat epilepsy. Several genetic association studies have been undertaken to examine the effect of a range of candidate genes for resistance. Although, few studies have explored the effect of the mutations into protein structure and biophysics in the epilepsy field. Much work remains to be done, but the plans made for exciting developments will hold therapeutic potential for patients with drug-resistance. In summary, we provide a critical review of the perspectives for the development of individualized medicine for epilepsy based on genetic polymorphisms/mutations in light of core elements such as transcriptomics, structural biology, disease model, pharmacogenomics and pharmacokinetics in a manner to improve the success of trial designs of antiepileptic drugs.

Early exercise promotes positive hippocampal plasticity and improves spatial memory in the adult life of rats.

There is a great deal of evidence showing the capacity of physical exercise to enhance cognitive function, reduce anxiety and depression, and protect the brain against neurodegenerative disorders. Although the effects of exercise are well documented in the mature brain, the influence of exercise in the developing brain has been poorly explored. Therefore, we investigated the morphological and functional hippocampal changes in adult rats submitted to daily treadmill exercise during the adolescent period. Male Wistar rats aged 21 postnatal days old (P21) were divided into two groups: exercise and control. Animals in the exercise group were submitted to daily exercise on the treadmill between P21 and P60. Running time and speed gradually increased over this period, reaching a maximum of 18 m/min for 60 min. After the aerobic exercise program (P60), histological and behavioral (water maze) analyses were performed. The results show that early-life exercise increased mossy fibers density and hippocampal expression of brain-derived neurotrophic factor and its receptor tropomyosin-related kinase B, improved spatial learning and memory, and enhanced capacity to evoke spatial memories in later stages (when measured at P96). It is important to point out that while physical exercise induces hippocampal plasticity, degenerative effects could appear in undue conditions of physical or psychological stress. In this regard, we also showed that the exercise protocol used here did not induce inflammatory response and degenerating neurons in the hippocampal formation of developing rats. Our findings demonstrate that physical exercise during postnatal development results in positive changes for the hippocampal formation, both in structure and function.

Malnutrition in infancy as a susceptibility factor for temporal lobe epilepsy in adulthood induced by the pilocarpine experimental model.

Malnutrition during the earliest stages of life may result in innumerable brain problems. Moreover, this condition could increase the chances of developing neurological diseases, such as epilepsy. We analyzed the effects of early-life malnutrition on susceptibility to epileptic seizures induced by the pilocarpine model of epilepsy. Wistar rat pups were kept on a starvation regimen from day 1 to day 21 after birth. At day 60, 16 animals (8 = well-nourished; 8 = malnourished) were exposed to the pilocarpine experimental model of epilepsy. Age-matched well-nourished (n = 8) and malnourished (n = 8) rats were used as controls. Animals were video-monitored over 9 weeks. The following behavioral parameters were evaluated: first seizure threshold (acute period of the pilocarpine model); status epilepticus (SE) latency; first spontaneous seizure latency (silent period), and spontaneous seizure frequency during the chronic phase. The cell and mossy fiber sprouting (MFS) density were evaluated in the hippocampal formation. Our results showed that the malnourished animals required a lower pilocarpine dose in order to develop SE (200 mg/kg), lower latency to reach SE, less time for the first spontaneous seizure and higher seizure frequency, when compared to well-nourished pilocarpine rats. Histopathological findings revealed a significant cell density reduction in the CA1 region and intense MFS among the malnourished animals. Our data indicate that early malnutrition greatly influences susceptibility to seizures and behavioral manifestations in adult life. These findings suggest that malnutrition in infancy reduces the threshold for epilepsy and promotes alterations in the brain that persist into adult life.

Early physical exercise and seizure susceptibility later in life.

We conducted a study to examine whether physical exercise undertaken during the period of postnatal brain development could modify seizure susceptibility later in life. Male Wistar rats aged 21 postnatal days (P21) were divided into two groups: exercise and control. Animals in the exercise group were submitted to daily exercise on the treadmill between P21 and P60. Running time and speed gradually increased over this period, reaching a maximum of 18 m/min for 60 min. After the final exercise session (P60), animals from exercise group were maintained non-trained for 90 days. This "period without stimulus" was used to observe the influence of early physical exercise on susceptibility to seizures induced by the pilocarpine model of epilepsy at P150. The results showed that the exercise program undertaken during the period of postnatal brain development delayed the onset and reduced the intensity of pilocarpine-induced motor symptoms in midlife rats. These findings suggest that early exercise interferes positively in the later ictogenesis process, and support the hypothesis that physical activity in early life may build a neural reserve against brain disorders.

The use of new world primates for biomedical research: an overview of the last four decades.

Animal experimentation contributes significantly to the progression of science. Nonhuman primates play a particularly important role in biomedical research not only because of their anatomical, physiological, biochemical, and behavioral similarities with humans but also because of their close phylogenetic affinities. In order to investigate the use of New World primates (NWP) in biomedical research over the last four decades (1966-2005), we performed a quantitative study of the literature listed in bibliographic databases from the Health Sciences. The survey was performed for each genus of NWP that has been bred in the National Center of Primates in Brazil. The number of articles published was determined for each genus and sorted according to the country from which the studies originated and the general scientific field. The data obtained suggests that Brazil is a leader in generating knowledge with NWP models for translational medicine.