Transcranial photobiomodulation changes neuronal morphology in the cerebral cortex of rats.

Transcranial photobiomodulation improves cerebral cortex metabolism. We hypothesized that chronic laser treatment may stimulate neuronal growth. To test this hypothesis, we investigated the morphology of neurons in the cerebral cortex of rats submitted to brief (2.5 min) daily sham or transcranial laser treatment (810 nm wavelength at 100 mW) for 58 consecutive days. Laser treatment increased the number of dendritic nodes and ends, and reduced the total dendritic length in neurons of the cerebral cortex. Taken together, our data indicate that chronic transcranial photobiomodulation induces morphological neuroplasticity in the cerebral cortex of rats.

Resistance exercise improves learning and memory and modulates hippocampal metabolomic profile in aged rats.

Physical activity has been considered an important non-medication intervention to preserve mnemonic processes during aging. However, how resistance exercise promotes such benefits remains unclear. A possible hypothesis is that brain-metabolic changes of regions responsible for memory consolidation is affected by muscular training. Therefore, we analyzed the memory, axiety and the metabolomic of aged male Wistar rats (19-20 months old in the 1st day of experiment) submitted to a 12-week resistance exercise protocol (EX, n = 11) or which remained without physical exercise (CTL, n = 13). Barnes maze, elevated plus maze and inhibitory avoidance tests were used to assess the animals' behaviour. The metabolomic profile was identified by nuclear magnetic resonance spectrometry. EX group had better performance in the tests of learning and spatial memory in Barnes maze, and an increase of short and long-term aversive memories formation in inhibitory avoidance. In addition, the exercised animals showed a greater amount of metabolites, such as 4-aminobutyrate, acetate, butyrate, choline, fumarate, glycerol, glycine, histidine, hypoxanthine, isoleucine, leucine, lysine, niacinamide, phenylalanine, succinate, tyrosine, valine and a reduction of ascorbate and aspartate compared to the control animals. These data indicate that the improvement in learning and memory of aged rats submitted to resistance exercise program is associated by changes in the hippocampal metabolomic profile.

Enriched environment and exercise effects on parvalbumin expression and distribution in the hippocampal formation of developing rats.

Several models of environmental enrichment and physical exercise have been used to explore the experience effects on brain functions and plasticity, mainly in adult animals. In order to examine the early influence of these stimuli on developing brain, the present study used calcium-binding protein parvalbumin as neuroplastic marker in the hippocampal formation of male Wistar rats subjected to environmental enrichment or physical exercise from postnatal days 21 to 60 (P21-P60). In our study, no significant difference in hippocampal expression and distribution of parvalbumin was found between enriched and control rats. However, a significant increase in parvalbumin protein expression as well as in the number of neurons stained with parvalbumin was observed in the hippocampal formation of rats submitted to daily treadmill exercise when compared to the control rats. The hippocampal region with the highest number of parvalbumin neurons in exercised rats was Cornus of Amon 2 e 3 (CA2/CA3). These findings indicate that developing brain may be differentially sensitive to environmental stimulation models. Specifically, our results show that hippocampal expression and distribution of parvalbumin in developing rats may be more influenced by exercise than by enriched environment. The mechanisms are not yet known.

Early exercise induces long-lasting morphological changes in cortical and hippocampal neurons throughout of a sedentary period of rats.

Life experiences at early ages, such as physical activity in childhood and adolescence, can result in long-lasting brain effects able to reduce future risk of brain disorders and to enhance lifelong brain functions. However, how early physical exercise promotes these effects remains unclear. A possible hypothesis is that physical exercise increases the expression of neurotrophic factors and stimulates neuronal growth, resulting in a neural reserve to be used at later ages. Basing our study on this hypothesis, we evaluated the absolute number and morphology of neuronal cells, as well as the expression of growth, proliferation and survival proteins (BDNF, Akt, mTOR, p70S6K, ERK and CREB) in the cerebral cortex and hippocampal formation throughout of a sedentary period of rats who were physically active during youth. To do this, male Wistar rats were submitted to an aerobic exercise protocol from the 21st to the 60th postnatal days (P21-P60), and evaluated at 0 (P60), 30 (P90) and 60 (P120) days after the last exercise session. Results showed that juvenile exercise increased, and maintained elevated, the number of cortical and hippocampal neuronal cells and dendritic arborization, when evaluated at the above post-exercise ages. Hippocampal BDNF levels and cortical mTOR expression were found to be increased at P60, but were restored to control levels at P90 and P120. Overall, these findings indicate that, despite the short-term effects on growth and survival proteins, early exercise induces long-lasting morphological changes in cortical and hippocampal neurons even during a sedentary period of rats.

Hippocampal distribution of parvalbumin neurons in female and male rats submitted to the same volume and intensity of aerobic exercise.

Several studies report the influence of gender on physical exercise-induced brain plasticity, including neurotrophic factor levels, neurogenesis, and navigation strategies in spatial memory task. However, it has been noted that females are physically more active than males in animal models of physical exercise. With this in mind, we conducted an experimental study to investigate the effect of sex on the brain of rats submitted to same volume and intensity of aerobic exercise. To do so, we used calcium-binding protein parvalbumin as neuroplastic marker to explore the hippocampal formation (a brain neurogenic/mnemonic region) of male and female rats submitted to 4 weeks of aerobic exercise on a treadmill at 12 m/min, 30 min per day. Our results show that, in both sexes, physical exercise increased hippocampal density of parvalbumin neurons in the cornus ammonis (CA1, CA2/3) and hilus subfields, but not in the dentate gyrus and subiculum. No difference in exercise-induced hipocampal parvalbumin density was found between male and female rats. These findings suggest that aerobic exercise promotes similar effects on hippocampal distribution of parvalbumin neurons of male and female rats, especially when they are submitted to the same volume and intensity of physical exercise.

Cortical and hippocampal expression of inflammatory and intracellular signaling proteins in aged rats submitted to aerobic and resistance physical training.

Aging is often accompanied by an increase in pro-inflammatory markers. This inflammatory process is directly related to cellular dysfunctions that induce events such as the exacerbated activation of cell death signaling pathways. In the aged brain, dysregulation of the normal activities of neuronal cells compromises brain functions, thereby favoring the onset of neurodegenerative diseases and cognitive deficits. Interactions between various stimuli, such as stress, are responsible for the modulation of cellular processes and activities. Physical exercise is a controllable model of stress, largely used as a strategy for studying the physiological mechanisms of inflammatory responses and their consequences. However, different types of physical exercise promote different responses in the organism. The present study was designed to investigate the expression of inflammatory cytokines and chemokines, and expression and activation of intracellular signaling proteins (CREB, ERK, Akt, p70S6k, STAT5, JNK, NFkB e p38) in the cerebral cortex and hippocampal formation of aged rats submitted to aerobic and resistance exercise. Inflammatory analysis showed that aged rats that underwent resistance training had decreased cortical levels of RANTES and a reduction in the hippocampal levels of MIP-2 when compared with control animals (sedentary). No significant difference was detected in the cortical and hippocampal inflammatory response between aerobic and sedentary groups. However, when comparing the two training models (aerobic vs resistance), it was observed that aerobic training increased the cortical levels of IL-13, IL-6, IL-17α compared with resistance training. Regarding the signaling proteins, a significant increase in cortical expression of the proteins JNK, ERK and p70S6k was found in the aerobic group in relation to the sedentary group. No significant change in the cortical and hippocampal expression of signaling proteins was detected between resistance training and sedentary groups. Nevertheless, when training models were compared, it was observed that aerobic training increased cortical expression of the total proteins p38, ERK, Akt and p70S6k in relation to resistance training. Taken together, these results show that changes in the brain expression of inflammatory and cell survival proteins in aged rats depend on the type of physical training.

Aerobic exercise in adolescence results in an increase of neuronal and non-neuronal cells and in mTOR overexpression in the cerebral cortex of rats.

Better cognitive performance and greater cortical and hippocampal volume have been observed in individuals who undertook aerobic exercise during childhood and adolescence. One possible explanation for these beneficial effects is that juvenile physical exercise enables better neural development and hence more cells and neuronal circuitries. It is probable that such effects occur through intracellular signaling proteins associated with cell growth, proliferation and survival. Based on this information, we evaluated the number of neuronal and non-neuronal cells using isotropic fractionation and the expression and activation of intracellular proteins (ERK, CREB, Akt, mTOR and p70S6K) in the cerebral cortex and hippocampal formation of the rats submitted to a physical exercise program on a treadmill during adolescence. Results showed that physical exercise increases the number of neuronal and non-neuronal cortical cells and hippocampal neuronal cells in adolescent rats. Moreover, mTOR overexpression was found in the cortical region of exercised adolescent rats. These findings indicate a significant cellular proliferative effect of aerobic exercise on the cerebral cortex in postnatal development.

Aerobic exercise reduces hippocampal ERK and p38 activation and improves memory of middle-aged rats.

Aging is often accompanied by cognitive decline, memory impairment, and an increased susceptibility to neurodegenerative disorders. Although the physiological processes of aging are not fully understood, these age-related changes have been interpreted by means of various cellular and molecular theories. Among these theories, alterations in the intracellular signaling pathways associated with cell growth, proliferation, and survival have been highlighted. Based on these observations and on recent evidence showing the beneficial effects of exercise on cognitive function in the elderly, we investigated the cell signaling pathways in the hippocampal formation of middle-aged rats (18 months old) submitted to treadmill exercise over 10 days. To do this, we evaluated the hippocampal activation of intracellular signaling proteins linked to cell growth, proliferation, and survival, such as Akt, mTOR, p70S6K, ERK, CREB, and p38. We also explored the cognitive performance (inhibitory avoidance) of middle-aged rats. It was found that physical exercise reduces ERK and p38 activation in the hippocampal formation of aged rats, when compared to the control group. The hippocampal activation and expression of Akt, mTOR, p70S6K, and CREB were not statistically different between the groups. It was also observed that aged rats from the exercise group exhibited better cognitive performance in the inhibitory avoidance task (aversive memory) than aged rats from the control group. Our results indicate that physical exercise reduces intracellular signaling pathways linked to inflammation and cell death (i.e., ERK and p38) and improves memory in middle-aged rats.