Sérgio Gomes da Silva

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.

Evaluation of physical activity habits in patients with posttraumatic stress disorder.

OBJECTIVE In this study, we present data from a survey that aimed to assess the physical activity habits of adult Brazilian patients with Posttraumatic Stress Disorder. METHOD Fifty male and female patients with Posttraumatic Stress Disorder participated in this study. The mean age at onset was 37±12 years, and the mean time between diagnosis and follow-up was 3.6±4.2 years. RESULTS Substantial changes in physical activity habits were observed following the onset of PTSD. While more than half of the patients participated in physical activities prior to Posttraumatic Stress Disorder onset, there was a significant reduction in their participation afterwards. The justifications for stopping physical activities or sport participation were lack of time and lack of motivation. DISCUSSION Several studies have shown that physical exercise decreases reverts symptoms of psychiatric disorders such as depression, anxiety and social isolation. We could therefore hypothesize that patients with Posttraumatic Stress Disorder who exercise should experience the same benefits. CONCLUSION Our findings demonstrated that patients with Posttraumatic Stress Disorder have low levels of participation in sports or physical activities.

The potential role of physical exercise in the treatment of epilepsy

The beneficial effects of exercise for people with epilepsy, including reduction of seizure susceptibility, improvement of quality of life, reduction of anxiety and depression, and better social integration, have increasingly been reported. We present data from human and animal studies supporting the role of exercise as a therapy for epilepsy complementary to standard treatments.

Physical exercise during the adolescent period of life increases hippocampal parvalbumin expression

In order to investigate whether physical exercise during development would promote changes the calcium-binding protein parvalbumin (PV) expression in the hippocampal formation, we performed an immunostaining study after an aerobic exercise program in rats during adolescent period of life. Wistar rats were submitted to daily exercise program in a treadmill between postnatal day 21 and 60. Running time and speed were gradually increased during the subsequent days until 18m/min for 60min. After the aerobic exercise program, animals of all groups were killed and PV immunostaining procedures were performed. The results showed significant increase of protein level in the hippocampal formation and PV-immunoreactive neurons in CA1 and CA2/CA3 regions of rats submitted to exercise when compared with control rats. This finding indicates that aerobic exercise program during adolescent period promotes neuroplastic changes in hippocampal formation.

Exercise-induced hippocampal anti-inflammatory response in aged rats

Aging is often accompanied by cognitive decline, memory impairment and an increased susceptibility to neurodegenerative disorders. Most of these age-related alterations have been associated with deleterious processes such as changes in the expression of inflammatory cytokines. Indeed, higher levels of pro-inflammatory cytokines and lower levels of anti-inflammatory cytokines are found in the aged brain. This perturbation in pro- and anti-inflammatory balance can represent one of the mechanisms that contribute to age-associated neuronal dysfunction and brain vulnerability. We conducted an experimental study to investigate whether an aerobic exercise program could promote changes in inflammatory response in the brains of aged rats. To do so, we evaluated the levels of tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL1β), interleukin 6 (IL6) and interleukin 10 (IL10) in the hippocampal formation of 18 month old rats that underwent treadmill training over 10 consecutive days. Quantitative immunoassay analyses showed that the physical exercise increased anti-inflammatory cytokine levels IL10 in the hippocampal formation of aged rats, when compared to the control group. The hippocampal levels of pro-inflammatory cytokines IL1β, IL6 and TNFα were not statistically different between the groups. However, a significant reduction in IL1β/IL10, IL6/IL10 and TNFα/IL10 ratio was observed in the exercised group in relation to the control group. These findings indicate a favorable effect of physical exercise in the balance between hippocampal pro- and anti-inflammatory during aging, as well as reinforce the potential therapeutic of exercise in reducing the risk of neuroinflammation-linked disorders.

Exercise paradigms to study brain injury recovery in rodents.

Exercise has been found to influence molecular systems important for maintaining neural function and plasticity as well as treatment of neurologic disorders. The stimuli required to elicit plasticity are thought to be activity dependent. Several protocols of physical exercise have been used to explore its effects on brain function. However, it is becoming increasingly recognized that no single physical exercise model is likely to fulfill all therapeutic needs. Varied interpretations of data derived from animal models have given rise to the lack of uniformity in the description and control of various features of the physical exercise stimulus, ranging from low to high intensity, intermittent to sustained, short to long durations, and different modes of activity. This article first describes the characteristics of the most frequently used animal models and goes on to review brain plasticity in intact animals and the usefulness of these models for the study of brain disorders. In this regard, animal models that investigate the beneficial effects of exercise on the brain before and after brain injury are discussed. A challenge for future studies is to better evaluate the usefulness of physical exercise protocols for preventing or treating brain disorders.

Differential effects of exercise intensities in hippocampal BDNF, inflammatory cytokines and cell proliferation in rats during the postnatal brain development

It has been established that low intensities of exercise produce beneficial effects for the brain, while high intensities can cause some neuronal damage (e.g. exacerbated inflammatory response and cell death). Although these effects are documented in the mature brain, the influence of exercise intensities in the developing brain has been poorly explored. To investigate the impact of exercise intensity in developing rats, we evaluated the hippocampal level of brain derived neurotrophic factor (BDNF), inflammatory cytokines (TNFα, IL6 and IL10) and the occurrence of hippocampal cell degeneration and proliferation at different stages of postnatal brain development of rats submitted to two physical exercise intensities. To this point, male rats were divided into different age groups: P21, P31, P41 and P51. Each age group was submitted to two exercise intensities (low and high) on a treadmill over 10 consecutive days, except the control rats. We verified that the density of proliferating cells was significantly higher in the dentate gyrus of rats submitted to low-intensity exercise from P21 to P30 compared with high-intensity exercise and control rats. A significant increase of proliferative cell density was found in rats submitted to high-intensity exercise from P31 to P40 when compared to low-intensity exercise and control rats. Elevated hippocampal levels of IL6 were detected in rats submitted to high-intensity exercise from P21 to P30 compared to control rats. From P41 to P50 period, higher levels of BDNF, TNFα and IL10 were found in the hippocampal formation of rats submitted to high-intensity exercise in relation to their control rats. Our data show that exercise-induced neuroplastic effects on BDNF levels and cellular proliferation in the hippocampal region are dependent on exercise intensity and developmental period. Thus, exercise intensity is an inflammation-inducing factor and exercise-induced inflammatory response during the postnatal brain development is also related to developmental stage. Our findings indicate that neuroplastic changes induced by exercise in developing rats depend on both age and training intensity.

Hippocampal mossy fiber sprouting induced by forced and voluntary physical exercise.

Alterations in the function and organization of synapses have been proposed to induce learning and memory. Previous studies have demonstrated that mossy fiber induced by overtraining in a spatial learning task can be related with spatial long-term memory formation. In this work we analyzed whether physical exercise could induce mossy fiber sprouting by using a zinc-detecting histologic technique (Timm). Rats were submitted to 3 and 5days of forced or voluntary exercise. Rat brains were processed for Timms staining to analyze mossy fiber projection at 7, 12 and 30days after the last physical exercise session. A significant increase of mossy fiber terminals in the CA3 stratum oriens region was observed after 5days of forced or voluntary exercise. Interestingly, the pattern of Timms staining in CA3 mossy fibers was significantly altered when analyzed 12days after exercise but not at 7days post-exercise. In contrast, animals trained for only 3days did not show increments of mossy fiber terminals in the stratum oriens. Altogether, these results demonstrate that sustained or programmed exercise can alter mossy fiber sprouting. Further Investigations are necessary to determine whether mossy fiber sprouting induced by exercise is also involved in learning and memory processes.

Maternal Exercise during Pregnancy Increases BDNF Levels and Cell Numbers in the Hippocampal Formation but Not in the Cerebral Cortex of Adult Rat Offspring

Clinical evidence has shown that physical exercise during pregnancy may alter brain development and improve cognitive function of offspring. However, the mechanisms through which maternal exercise might promote such effects are not well understood. The present study examined levels of brain-derived neurotrophic factor (BDNF) and absolute cell numbers in the hippocampal formation and cerebral cortex of rat pups born from mothers exercised during pregnancy. Additionally, we evaluated the cognitive abilities of adult offspring in different behavioral paradigms (exploratory activity and habituation in open field tests, spatial memory in a water maze test, and aversive memory in a step-down inhibitory avoidance task). Results showed that maternal exercise during pregnancy increased BDNF levels and absolute numbers of neuronal and non-neuronal cells in the hippocampal formation of offspring. No differences in BDNF levels or cell numbers were detected in the cerebral cortex. It was also observed that offspring from exercised mothers exhibited better cognitive performance in nonassociative (habituation) and associative (spatial learning) mnemonic tasks than did offspring from sedentary mothers. Our findings indicate that maternal exercise during pregnancy enhances offspring cognitive function (habituation behavior and spatial learning) and increases BDNF levels and cell numbers in the hippocampal formation of offspring.

Knowledge about epilepsy among health professionals: a cross-sectional survey in São Paulo, Brazil

Objective To evaluate the epilepsy knowledge among health professionals in São Paulo, Brazil. Design This is a cross-sectional study. Participants Professionals with academic degrees in physical education (n=134), nutrition (n=116), medicine (n=100), psychology (n=53), nursing (n=122) and physiotherapy (n=99) who lived in São Paulo City, Brazil. Primary and secondary outcome measures Knowledge of health professionals about epilepsy. Methods Professionals with academic degrees in physical education (n=134), nutrition (n=116), medicine (n=100), psychology (n=53), nursing (n=122) and physiotherapy (n=99) who lived in São Paulo City, Brazil, were invited to participate in the study. The subjects (n=624) answered a questionnaire composed of 25 simple closed-ended questions from three areas: personal, educational and knowledge. Results Out of all subjects, 88.5% (n=552) had a postgraduate education, while 11.5% (n=72) had only an undergraduate degree. The authors found that physical educators, nutritionists and physiotherapists received lower scores on their epilepsy knowledge than other health professionals. Conclusions Health professionals are considered better-educated group inside the society, especially with regards to healthcare issues. Thus, it is important they also have an accurate and correct knowledge about epilepsy. The findings of the present study indicate an imperative improvement in education about epilepsy, as well as an inclusion of formal programmes for epilepsy education especially for non-medical professionals. An improvement in epilepsy education might contribute to an improvement in epilepsy care and management.