Ricardo C. Cassilhas

SPATIAL MEMORY IS IMPROVED BY AEROBIC AND RESISTANCE EXERCISE THROUGH DIVERGENT MOLECULAR MECHANISMS

A growing body of scientific evidence indicates that exercise has a positive impact on human health, including neurological health. Aerobic exercise, which is supposed to enhance cardiovascular functions and metabolism, also induces neurotrophic factors that affect hippocampal neurons, thereby improving spatial learning and memory. Alternatively, little is known about the effect of resistance exercise on hippocampus-dependent memory, although this type of exercise is increasingly recommended to improve muscle strength and bone density and to prevent age-related disabilities. Therefore, we evaluated the effects of resistance training on spatial memory and the signaling pathways of brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1), comparing these effects with those of aerobic exercise. Adult male Wistar rats underwent 8 weeks of aerobic training on a treadmill (AERO group) or resistance training on a vertical ladder (RES group). Control and sham groups were also included. After the training period, both AERO and RES groups showed improved learning and spatial memory in a similar manner. However, both groups presented distinct signaling pathways. Although the AERO group showed increased level of IGF-1, BDNF, TrkB, and β-CaMKII (calcium/calmodulin-dependent kinase II) in the hippocampus, the RES group showed an induction of peripheral and hippocampal IGF-1 with concomitant activation of receptor for IGF-1 (IGF-1R) and AKT in the hippocampus. These distinct pathways culminated in an increase of synapsin 1 and synaptophysin expression in both groups. These findings demonstrated that both aerobic and resistance exercise can employ divergent molecular mechanisms but achieve similar results on learning and spatial memory.

Exercício físico e função cognitiva: uma revisão

RESUMO O exercicio e o treinamento fisico sao conhecidos por promover diversas alteracoes, incluindo beneficios cardiorrespiratorios, aumento da densidade mineral ossea e diminuicao do risco de doencas cronico-degenerativas. Recentemente outro aspecto tem ganhando notoriedade: trata-se da melhoria na funcao cognitiva. Embora haja grande controversia, diversos estudos tem demonstrado que o exercicio fisico melhora e protege a funcao cerebral, sugerindo que pessoas fisicamente ativas apresentam menor risco de serem acometidas por desordens mentais em relacao as sedentarias. Isso mostra que a participacao em programas de exercicios fisicos exercem beneficios nas esferas fisica e psicologica e que, provavelmente, individuos fisicamente ativos possuem um processamento cognitivo mais rapido. Embora os beneficios cognitivos do estilo de vida fisicamente ativo parecam estar relacionados ao nivel de atividade fisica regular, ou seja, exercicio realizado durante toda a vida, sugerindo uma “reserva cognitiva”, nunca e tarde para se iniciar um programa de exercicios fisicos. Dessa forma, o uso do exercicio fisico como alternativa para melhorar a funcao cognitiva parece ser um objetivo a ser alcancado, principalmente em virtude da sua aplicabilidade, pois se trata de um metodo relativamente barato, que pode ser direcionado a grande parte da populacao. Assim, o objetivo da presente revisao e o de discutir os aspectos associativos entre exercicio fisico e funcao cognitiva, permitindo uma ponderacao entre o seu uso enquanto alternativa e elemento coadjuvante.

Mood, Anxiety, and Serum IGF-1 in Elderly Men Given 24 Weeks of High Resistance Exercise:

As aging advances, changes in mood and anxiety may imply greater risk of mood disorders, particularly anxiety and depression. Resistance exercise reduces anxiety and lessens risk of depression in the elderly, but little is known of the mechanisms involved. It was hypothesized that the human growth factor (IGF-1) may improve mood and anxiety in elderly participants given resistance training. 43 elderly men ages 65 to 75 years were randomly assigned to two groups, Control (n = 23) and high resistance Exercise (n = 20). After 24 wk., the Exercise group showed improved muscular strength and higher IGF-1 serum levels than the Control group, as indicated by mean scores on a visual analogue mood scale and the State-Trait Anxiety Inventory. Intensive resistance training was efficacious in improving mood, anxiety, and IGF-1 serum concentration in elderly individuals free of clinical mood disorders.

Physical exercise, neuroplasticity, spatial learning and memory

There has long been discussion regarding the positive effects of physical exercise on brain activity. However, physical exercise has only recently begun to receive the attention of the scientific community, with major interest in its effects on the cognitive functions, spatial learning and memory, as a non-drug method of maintaining brain health and treating neurodegenerative and/or psychiatric conditions. In humans, several studies have shown the beneficial effects of aerobic and resistance exercises in adult and geriatric populations. More recently, studies employing animal models have attempted to elucidate the mechanisms underlying neuroplasticity related to physical exercise-induced spatial learning and memory improvement, even under neurodegenerative conditions. In an attempt to clarify these issues, the present review aims to discuss the role of physical exercise in the improvement of spatial learning and memory and the cellular and molecular mechanisms involved in neuroplasticity.

The beneficial effects of strength exercise on hippocampal cell proliferation and apoptotic signaling is impaired by anabolic androgenic steroids

Previous studies have shown that strength exercise improves memory and increases expression of a myriad of proteins involved on neuronal survival and synaptic plasticity in the hippocampus. Conversely, chronic exposure to supraphysiological levels of anabolic androgenic steroids (AAS) can induce psychiatric abnormalities, cognitive deficits, impair neurotransmission, alter the levels of neurotrophic factors, decrease cell proliferation and neurogenesis, and enhance neuronal cell death. In the present study, we investigated the effects of the AAS nandrolone decanoate (ND) administration during a strength exercise program on cell proliferation, apoptotic status and brain-derived neurotrophic factor (BDNF) expression in the rat hippocampus. Adult male Wistar rats were subjected to 4 weeks of progressive strength exercise in a vertical ladder apparatus with or without daily doses (5.0 mg/kg, SC) of ND. Immunohistochemistry analysis revealed that strength exercise increased significantly the number of Ki-67-positive cells (a cell proliferation marker) in dentate gyrus (DG) of hippocampus. However, this effect was abrogated when strength exercise was combined with ND. Although western blot analysis of whole hippocampus showed no significant differences in Bax and Bcl-2 protein expression among groups, the immunoreactivity of the pro-apoptotic protein Bax was significantly increased in DG, CA1 and CA3 hippocampal subfields of sedentary rats treated with ND. Moreover, the increase in the immunoreactivity of anti-apoptotic protein Bcl-2 (DG and CA3) induced by strength exercise was diminished by ND. There were no significant differences in BDNF expression among experimental groups. Therefore, the present findings suggest that the beneficial effects of strength exercise on hippocampal cell proliferation and apoptotic signaling are impaired by ND.

A strength exercise program in rats with epilepsy is protective against seizures

The beneficial effects of physical exercise on epilepsy, such as a decreased seizure frequency, have been observed following aerobic exercise programs in both clinical and experimental studies. However, it is not well clarified whether other types of exercise, including strength exercise, can provide similar benefits for epilepsy. Forty four animals with epilepsy were continuously monitored 24 h a day for 60 days and divided into two periods of 30 days. The first period was used to determine the number of seizures before beginning the physical exercise program, and the second period was utilized to determine the number of seizures during the strength training. The mean frequency of seizures in the control and SHAM groups increased significantly from period 1 to period 2. Although the frequency of seizures did not change significantly between the two periods of 30 days of observation in the strength exercise group, a significant reduction in the seizure frequency was observed compared with the control and SHAM groups in period 2. Our study demonstrated that a strength exercise program exerted a significant influence on the seizure frequency in animals with epilepsy and strengthens the observed beneficial effect of exercise on epilepsy that has been demonstrated in animal studies. The finding of this nonclinical study can open a new window to verify the beneficial contribution of strength exercise in epilepsy. Further experimental and clinical investigations are necessary to explore the extent to which strength exercise interferes with the epileptic condition.

Resistance exercise improves hippocampus-dependent memory

It has been demonstrated that resistance exercise improves cognitive functions in humans. Thus, an animal model that mimics this phenomenon can be an important tool for studying the underlying neurophysiological mechanisms. Here, we tested if an animal model for resistance exercise was able to improve the performance in a hippocampus-dependent memory task. In addition, we also evaluated the level of insulin-like growth factor 1/insulin growth factor receptor (IGF-1/IGF-1R), which plays pleiotropic roles in the nervous system. Adult male Wistar rats were divided into three groups (N = 10 for each group): control, SHAM, and resistance exercise (RES). The RES group was submitted to 8 weeks of progressive resistance exercise in a vertical ladder apparatus, while the SHAM group was left in the same apparatus without exercising. Analysis of a cross-sectional area of the flexor digitorum longus muscle indicated that this training period was sufficient to cause muscle fiber hypertrophy. In a step-through passive avoidance task (PA), the RES group presented a longer latency than the other groups on the test day. We also observed an increase of 43 and 94% for systemic and hippocampal IGF-1 concentration, respectively, in the RES group compared to the others. A positive correlation was established between PA performance and systemic IGF-1 (r = 0.46, P < 0.05). Taken together, our data indicate that resistance exercise improves the hippocampus-dependent memory task with a concomitant increase of IGF-1 level in the rat model. This model can be further explored to better understand the effects of resistance exercise on brain functions.

A 20-week program of resistance or concurrent exercise improves symptoms of schizophrenia: results of a blind, randomized controlled trial.

OBJECTIVE To evaluate the effects of 20 weeks of resistance and concurrent training on psychotic and depressive symptoms, quality of life outcomes, and serum IGF-1, IGFBP-3, and brain-derived neurotrophic factor (BDNF) concentrations in patients with schizophrenia. METHODS In this blind, randomized controlled clinical trial, 34 patients with schizophrenia were assigned to one of three groups: control (CTRL, n=13), resistance exercise (RESEX, n=12), or concurrent exercise (CONCEX, n=9). Symptoms, quality of life, strength, and other variables were assessed. RESULTS A significant time-by-group interaction was found for the RESEX and CONCEX groups on the Positive and Negative Syndrome Scale (PANSS) total score for disease symptoms (p = 0.007), positive symptoms (p = 0.003), and on the arm extension one-repetition maximum (1RM) test (p = 0.016). In addition, significant improvements on negative symptoms (p = 0.027), on the role-physical domain of the Short Form-36 Health Survey (p = 0.019), and on the chest press 1RM test (p = 0.040) were observed in the RESEX group. No changes were observed for the other variables investigated. CONCLUSIONS In this sample of patients with schizophrenia, 20 weeks of resistance or concurrent exercise program improved disease symptoms, strength, and quality of life. ClinicalTrials.gov: NCT01674543.

Reviewing on physical exercise and the cognitive function

RESUMO O exercicio e o treinamento fisico sao conhecidos por promover diversas alteracoes, incluindo beneficios cardiorrespiratorios, aumento da densidade mineral ossea e diminuicao do risco de doencas cronico-degenerativas. Recentemente outro aspecto tem ganhando notoriedade: trata-se da melhoria na funcao cognitiva. Embora haja grande controversia, diversos estudos tem demonstrado que o exercicio fisico melhora e protege a funcao cerebral, sugerindo que pessoas fisicamente ativas apresentam menor risco de serem acometidas por desordens mentais em relacao as sedentarias. Isso mostra que a participacao em programas de exercicios fisicos exercem beneficios nas esferas fisica e psicologica e que, provavelmente, individuos fisicamente ativos possuem um processamento cognitivo mais rapido. Embora os beneficios cognitivos do estilo de vida fisicamente ativo parecam estar relacionados ao nivel de atividade fisica regular, ou seja, exercicio realizado durante toda a vida, sugerindo uma “reserva cognitiva”, nunca e tarde para se iniciar um programa de exercicios fisicos. Dessa forma, o uso do exercicio fisico como alternativa para melhorar a funcao cognitiva parece ser um objetivo a ser alcancado, principalmente em virtude da sua aplicabilidade, pois se trata de um metodo relativamente barato, que pode ser direcionado a grande parte da populacao. Assim, o objetivo da presente revisao e o de discutir os aspectos associativos entre exercicio fisico e funcao cognitiva, permitindo uma ponderacao entre o seu uso enquanto alternativa e elemento coadjuvante.

Animal model for progressive resistance exercise: a detailed description of model and its implications for basic research in exercise

The Several animal models have been proposed for resistance training. In addition, the results of these studies have been highly variable. Some of the studies have used negative reinforcement, electric shock or food deprivation to motivate the learning of the task. Features such as conditioning through electric shock may undermine the significance of the results or even prevent the model from being successfully executed. Due to these reasons, in this study we propose to use an adaptation of the vertical ladder climbing model for progressive resistance training in rats, albeit with a unique feature to ensure the homogeneity of the study groups: a period of adaptation to the apparatus without any negative reinforcement followed by a subsequent pairing of animals based on their ability to learn. The animals were distributed in the experimental group who were subjected to 8 weeks of a progressive resistance exercise protocol and the control group. After 8wks, the gastrocnemius, soleus, flexor digitorum longus (FDL), and plantaris muscles were removed and the cross-sectional area morphometry was obtened. The animals from experimental group showed hypertrophy [F(4, 15)=17,404, P < 0.001] for gastrocnemius [60% of hipertrophy; Control (2628,64 ± 348,50) versus Experimental (4207,77 ± 1256,52); ES=1.96; Power=0,86]; FDL [35% of hipertrophy; Control (2753,80 ± 359,54) versus Experimental (3711,84 ± 279,45); ES=2.99; Power=0.99] and plantaris [38% of hipertrophy; Control (2730,44 ± 320,56) versus Experimental (3767,30 ± 625,80); ES=2.19; Power=0.92], without modifications for soleus. All animals successfully completed the 8-week progressive resistance training program without any injuries, abandonment or death. Negative reinforcements such as electric shock were not required at any time in the experiment. In conclusion, we showed an adaptation of the previus model for progressive resistance training in rats. A period of adaptation to the apparatus without any negative reinforcement followed by a subsequent pairing of animals based on their ability to learn may be a alternative strategy for the original protocol. We also observed hypertrophy (gastrocnemius, FDL, and plantaris) showed the vality of this procolos for resistance exercise issues. The results of this study may be useful in basic/ applied neuroscience research and resistance exercise.