Storytelling increases oxytocin and positive emotions and decreases cortisol and pain in hospitalized children.

Storytelling is a distinctive human characteristic that may have played a fundamental role in humans' ability to bond and navigate challenging social settings throughout our evolution. However, the potential impact of storytelling on regulating physiological and psychological functions has received little attention. We investigated whether listening to narratives from a storyteller can provide beneficial effects for children admitted to intensive care units. Biomarkers (oxytocin and cortisol), pain scores, and psycholinguistic associations were collected immediately before and after storytelling and an active control intervention (solving riddles that also involved social interaction but lacked the immersive narrative aspect). Compared with the control group, children in the storytelling group showed a marked increase in oxytocin combined with a decrease in cortisol in saliva after the 30-min intervention. They also reported less pain and used more positive lexical markers when describing their time in hospital. Our findings provide a psychophysiological basis for the short-term benefits of storytelling and suggest that a simple and inexpensive intervention may help alleviate the physical and psychological pain of hospitalized children on the day of the intervention.

Stress symptoms occur in patients undergoing chemotherapy treatment independently of the level of physical activity.

The cancer patient is undergoing a set of procedures that affect the physical and psychological balance, which can generate stressful situations in the organism. In turn, physical activity helps to treat stress, promoting well-being and reducing anxiety. Our study aimed to verify the influence of physical activity practice on stress symptoms in patients undergoing oncological chemotherapy treatment. For this, we used Lipp's Inventory of Stress Symptoms (ISSL) and the International Physical Activity Questionnaire (IPAQ) in 56 patients with cancer. Our data show that 45.4% of the participants exhibited stress scores, of which, 21.8% were at near to exhaustion, and 23.6% at exhaustion. We observed that 30% of them are considered sufficiently active, 25% insufficiently active, 45% sedentary. No association was observed between physical activity and stress. These findings indicate that stress symptoms occur in patients undergoing chemotherapy treatment regardless of the level of physical activity.

Improved Spatial Memory And Neuroinflammatory Profile Changes in Aged Rats Submitted to Photobiomodulation Therapy.

Recent evidences have shown the therapeutic potential of transcranial photobiomodulation on traumatic brain injury and Alzheimer's disease. Despite the promising benefits in the brain, little is known about the laser's effects in the absence of pathological conditions. We submitted young (4 months old) and aged (20 months old) rats to transcranial low-level laser and evaluated their exploratory activity and habituation in open field, anxiety in elevated plus maze, spatial memory in Barnes maze, and aversive memory in a step-down inhibitory avoidance task. Additionally, the levels of a panel of inflammatory cytokines and chemokines were quantified in two different brain regions: the cerebral cortex and the hippocampus. Young and aged rats submitted to transcranial laser exhibited better cognitive performance in Barnes maze than did control rats. Transcranial laser therapy decreased cortical levels of GM-CSF, IL-10, MCP-1, LIX, and TNFα in young rats and IL-5 in aged rats. High levels of IL-6, IL-10, and TNF-alpha were found in the cerebral cortex of aged rats submitted to transcranial laser. In the hippocampus, a decrease in IP-10 and fractalkine levels was observed in the aged rats from the laser group when compared to the aged rats from the control group. Our data indicate that transcranial photobiomodulation improves spatial learning and memory and alters the neuroinflammatory profile of young and aged rats' brains.

Physical exercise alters the activation of downstream proteins related to BDNF-TrkB signaling in male Wistar rats with epilepsy.

There are a considerable number of studies concerning the behavioral effects of physical exercise on the epileptic brain; however, the intracellular signaling mechanisms involved remain unclear. We investigated the effects of aerobic exercise on hippocampal levels of brain-derived neurotrophic factor (BDNF), expression of its receptor tropomyosin receptor kinase B (TrkB), and activation of intracellular proteins related to BDNF-TrkB signaling in male Wistar rats with pilocarpine-induced epilepsy. Thirty days after the first spontaneous seizure, rats from the exercise group undertook a 30-day physical exercise program on the treadmill. Thereafter, BDNF levels, expression of TrkB, and activation of intracellular proteins were quantified by enzyme-linked immunosorbent assay, Western blotting, and multiplex assay, respectively. Statistical analyses were conducted using nonparametric tests. Rats with epilepsy presented decreased BDNF levels compared with control rats. BDNF levels increased significantly in the exercise group compared with the epileptic and control groups. Expression of full-length and truncated TrkB was increased in rats with epilepsy, and physical exercise restored its expression to control levels. RAC-alpha serine/threonine-protein kinase, mammalian target of rapamycin, and extracellular signal-regulated kinase activation were reduced in rats with epilepsy, and exercise increased activation compared with control and epilepsy groups. Increased cAMP response element binding protein activation was observed in the exercise group compared with the epilepsy group. Our findings indicate that the beneficial effects of exercise in the epileptic brain can be in part related to alterations in the activation of proteins related to the BDNF-TrkB signaling pathway.

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.

Resistance Exercise Reduces Seizure Occurrence, Attenuates Memory Deficits and Restores BDNF Signaling in Rats with Chronic Epilepsy.

Epilepsy is a disease characterized by recurrent, unprovoked seizures. Cognitive impairment is an important comorbidity of chronic epilepsy. Human and animal model studies of epilepsy have shown that aerobic exercise induces beneficial structural and functional changes and reduces the number of seizures. However, little is yet understood about the effects of resistance exercise on epilepsy. We evaluated the effects of a resistance exercise program on the number of seizures, long-term memory and expression/activation of signaling proteins in rats with epilepsy. The number of seizures was quantified by video-monitoring and long-term memory was assessed by an inhibitory avoidance test. Using western blotting, multiplex and enzyme-linked immunosorbent assays, we determined the effects of a 4-week resistance exercise program on IGF-1 and BDNF levels and ERK, CREB, mTOR activation in the hippocampus of rats with epilepsy. Rats with epilepsy submitted to resistance exercise showed a decrease in the number of seizures compared to non-exercised epileptic rats. Memory deficits were attenuated by resistance exercise. Rats with epilepsy showed an increase in IGF-1 levels which were restored to control levels by resistance exercise. BDNF levels and ERK and mTOR activation were decreased in rats with epilepsy and resistance exercise restored these to control levels. In conclusion, resistance exercise reduced seizure occurrence and mitigated memory deficits in rats with epilepsy. These resistance exercise-induced beneficial effects can be related to changes in IGF-1 and BDNF levels and its signaling protein activation. Our findings indicate that the resistance exercise might be included as complementary therapeutic strategy for epilepsy treatment.

Differential effects of exercise on brain opioid receptor binding and activation in rats.

Physical exercise stimulates the release of endogenous opioid peptides supposed to be responsible for changes in mood, anxiety, and performance. Exercise alters sensitivity to these effects that modify the efficacy at the opioid receptor. Although there is evidence that relates exercise to neuropeptide expression in the brain, the effects of exercise on opioid receptor binding and signal transduction mechanisms downstream of these receptors have not been explored. Here, we characterized the binding and G protein activation of mu opioid receptor, kappa opioid receptor or delta opioid receptor in several brain regions following acute (7 days) and chronic (30 days) exercise. As regards short- (acute) or long-term effects (chronic) of exercise, overall, higher opioid receptor binding was observed in acute-exercise animals and the opposite was found in the chronic-exercise animals. The binding of [(35) S]GTPγS under basal conditions (absence of agonists) was elevated in sensorimotor cortex and hippocampus, an effect more evident after chronic exercise. Divergence of findings was observed for mu opioid receptor, kappa opioid receptor, and delta opioid receptor receptor activation in our study. Our results support existing evidence of opioid receptor binding and G protein activation occurring differentially in brain regions in response to diverse exercise stimuli. We characterized the binding and G protein activation of mu, kappa, and delta opioid receptors in several brain regions following acute (7 days) and chronic (30 days) exercise. Higher opioid receptor binding was observed in the acute exercise animal group and opposite findings in the chronic exercise group. Higher G protein activation under basal conditions was noted in rats submitted to chronic exercise, as visible in the depicted pseudo-color autoradiograms.

Parvalbumin expression and distribution in the hippocampal formation of Cebus apella.

New World primates play an important role in biomedical research. However, the literature still lacks information on many structural features of the brain in these species, particularly structures of the hippocampal formation that are related to long-term memory storage. This study was designed to provide information, for the first time, about the distribution and number of neurons expressing parvalbumin-immunoreactivity (PV-I) in the subregions of the hippocampal formation in Cebus apella, a New World primate species commonly used in biomedical research. Our results revealed that for several morphometric variables, PV-I cells differ significantly among the subregions CA1, CA2, CA3, and the hilus. Based upon our findings and those of other studies, we hypothesize that the proportional increase from monkeys to humans in PV-I cell density within CA1 is a factor contributing to the evolution of increased memory formation and storage.

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 (IL1ß), 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 IL1ß, IL6 and TNFα were not statistically different between the groups. However, a significant reduction in IL1ß/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.

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.

Photobiomodulation for the treatment of neuroinflammation: A systematic review of controlled laboratory animal studies.

Background: Neuroinflammation is a response that involves different cell lineages of the central nervous system, such as neurons and glial cells. Among the non-pharmacological interventions for neuroinflammation, photobiomodulation (PBM) is gaining prominence because of its beneficial effects found in experimental brain research. We systematically reviewed the effects of PBM on laboratory animal models, specially to investigate potential benefits of PBM as an efficient anti-inflammatory therapy. Methods: We conducted a systematic search on the bibliographic databases (PubMed and ScienceDirect) with the keywords based on MeSH terms: photobiomodulation, low-level laser therapy, brain, neuroinflammation, inflammation, cytokine, and microglia. Data search was limited from 2009 to June 2022. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The initial systematic search identified 140 articles. Among them, 54 articles were removed for duplication and 59 articles by screening. Therefore, 27 studies met the inclusion criteria. Results: The studies showed that PBM has anti-inflammatory properties in several conditions, such as traumatic brain injury, edema formation and hyperalgesia, ischemia, neurodegenerative conditions, aging, epilepsy, depression, and spinal cord injury. Conclusion: Taken together, these results indicate that transcranial PBM therapy is a promising strategy to treat brain pathological conditions induced by neuroinflammation.

Photobiomodulation of Cytochrome c Oxidase by Chronic Transcranial Laser in Young and Aged Brains.

In cellular bioenergetics, cytochrome c oxidase (CCO) is the enzyme responsible for oxygen consumption in the mitochondrial electron transport chain, which drives oxidative phosphorylation for adenosine triphosphate (ATP) production. CCO is also the major intracellular acceptor of photons in the light wavelengths used for photobiomodulation (PBM). Brain function is critically dependent on oxygen consumption by CCO for ATP production. Therefore, our objectives were (1) to conduct the first detailed brain mapping study of the effects of PBM on regional CCO activity, and (2) to compare the chronic effects of PBM on young and aged brains. Specifically, we used quantitative CCO histochemistry to map the differences in CCO activity of brain regions in healthy young (4 months old) and aged (20 months old) rats from control groups with sham stimulation and from treated groups with 58 consecutive days of transcranial laser PBM (810 nm wavelength and 100 mW power). We found that aging predominantly decreased regional brain CCO activity and systems-level functional connectivity, while the chronic laser stimulation predominantly reversed these age-related effects. We concluded that chronic PBM modified the effects of aging by causing the CCO activity on brain regions in laser-treated aged rats to reach levels similar to those found in young rats. Given the crucial role of CCO in bioenergetics, PBM may be used to augment brain and behavioral functions of older individuals by improving oxidative energy metabolism.

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.

Photobiomodulation Improves the Inflammatory Response and Intracellular Signaling Proteins Linked to Vascular Function and Cell Survival in the Brain of Aged Rats.

Photobiomodulation is a non-pharmacological tool widely used to reduce inflammation in many tissues. However, little is known about its effects on the inflammatory response in the aged brain. We conducted the study to examine anti-inflammatory effects of photobiomodulation in aging brains. We used aged rats (20 months old) with control (handled, laser off) or transcranial laser (660 nm wavelength, 100 mW power) treatments for 10 consecutive days and evaluated the level of inflammatory cytokines and chemokines, and the expression and activation of intracellular signaling proteins in the cerebral cortex and the hippocampus. Inflammatory analysis showed that aged rats submitted to transcranial laser treatment had increased levels of IL-1alpha and decreased levels of IL-5 in the cerebral cortex. In the hippocampus, the laser treatment increased the levels of IL-1alpha and decreased levels of IL-5, IL-18, and fractalkine. Regarding the intracellular signaling proteins, a reduction in the ERK and p38 expression and an increase in the STAT3 and ERK activation were observed in the cerebral cortex of aged rats from the laser group. In addition, the laser treatment increased the hippocampal expression of p70S6K, STAT3, and p38 of aged rats. Taken together, our data indicate that transcranial photobiomodulation can improve the inflammatory response and the activation of intracellular signaling proteins linked to vascular function and cell survival in the aged brain.

Effect of the ACTN-3 gene polymorphism on functional fitness and executive function of elderly.

During aging, physical integrity and cognitive abilities, especially executive function, become compromised, directly influencing the quality of life of the elderly. One good strategy to ensure healthy aging is the practice of physical exercise. Activities to improve aerobic capacity and muscle strength are extremely important in old age. However, some genetic factors can interfere both positively and negatively with these gains. In this context, the polymorphism rs1815739 (R577X) of the α-actinin 3 gene (ACTN-3) is commonly studied and related to muscle phenotype. Thus, the present study aimed to investigate the effect of the ACTN-3 gene polymorphism on the functional fitness (measured by the Senior Fit test) and cognitive capacity (evaluated by the Stroop test) of the elderly (n = 347), both men and women. We did not find the effect of genotype on functional fitness, but we did observed a positive effect of the ACTN-3 gene polymorphism on executive function. The presence of the X allele of the ACTN3 gene in the elderly was related to a better performance in the Stroop test (shorter answer time). Our results showed that ACTN-3 gene polymorphism affects the executive function of the elderly but not their functional fitness.

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.

Hippocampal plasticity in rats submitted to a gastric restrictive procedure.

Bariatric surgery has been the most effective therapeutic intervention for morbidly obese patients. However, recent evidence has shown that this procedure may cause serious neurological complications such as Wernicke encephalopathy, depression, and memory impairment. With this in mind, we conducted an experimental study to investigate whether weight-reduction surgery would promote morphological changes in the hippocampal formation, a brain region linked to cognitive and emotional processes. To do so, the present study evaluated the hippocampal expression of parvalbumin interneurons in rats submitted to a gastric restrictive procedure (experimental phytobezoar). Our results demonstrated that rats with gastric-reduced capacity presented a significant increase in the expression of the parvalbumin interneurons in the hippocampal CA1 and CA3 subfields. These data are the first experimental evidence that restrictive bariatric surgery may alter hippocampal cytoarchitecture.

Photobiomodulation for the aging brain.

Longevity is one of the great triumphs of humanity. Worldwide, the elderly is the fastest growing segment of the population. As a consequence, the number of cases of age-related cognitive decline and neurological diseases associated with aging, such as Alzheimer's and Parkinson's, has been increasing. Among the non-pharmacological interventions studied for the treatment or prevention of age-related neurocognitive impairment, photobiomodulation (PBM) has gained prominence for its beneficial effects on brain functions relevant to aging brains. In animal models, the neuroprotective and neuromodulatory capacity of PBM has been observed. Studies using both animals and humans have shown promising metabolic and hemodynamic effects of PBM on the brain, such as improved mitochondrial and vascular functions. Studies in humans have shown that PBM can improve electrophysiological activity and cognitive functions such as attention, learning, memory and mood in older people. In this paper we will review the main brain effects of PBM during aging, discuss its mechanisms of action relevant to the aging brain, and call for more controlled studies in older populations.

Transcranial Laser Photobiomodulation Improves Intracellular Signaling Linked to Cell Survival, Memory and Glucose Metabolism in the Aged Brain: A Preliminary Study.

Aging is often accompanied by exacerbated activation of cell death-related signaling pathways and decreased energy metabolism. We hypothesized that transcranial near-infrared laser may increase intracellular signaling pathways beneficial to aging brains, such as those that regulate brain cell proliferation, apoptosis, and energy metabolism. To test this hypothesis, we investigated the expression and activation of intracellular signaling proteins in the cerebral cortex and hippocampus of aged rats (20 months old) treated with the transcranial near-infrared laser for 58 consecutive days. As compared to sham controls, transcranial laser treatment increased intracellular signaling proteins related to cell proliferation and cell survival, such as signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), p70 ribosomal protein S6 kinase (p70S6K) and protein kinase B (PKB), also known as Akt that is linked to glucose metabolism. In addition, ERK is linked to memory, while ERK and JNK signaling pathways regulate glucose metabolism. Specifically, the laser treatment caused the activation of STAT3, ERK, and JNK signaling proteins in the cerebral cortex. In the hippocampus, the laser treatment increased the expression of p70S6K and STAT3 and the activation of Akt. Taken together, the data support the hypothesis that transcranial laser photobiomodulation improves intracellular signaling pathways linked to cell survival, memory, and glucose metabolism in the brain of aged rats.

Effects of Chronic Photobiomodulation with Transcranial Near-Infrared Laser on Brain Metabolomics of Young and Aged Rats.

Since laser photobiomodulation has been found to enhance brain energy metabolism and cognition, we conducted the first metabolomics study to systematically analyze the metabolites modified by brain photobiomodulation. Aging is often accompanied by cognitive decline and susceptibility to neurodegeneration, including deficits in brain energy metabolism and increased susceptibility of nerve cells to oxidative stress. Changes in oxidative stress and energetic homeostasis increase neuronal vulnerability, as observed in diseases related to brain aging. We evaluated and compared the cortical and hippocampal metabolic pathways of young (4 months old) and aged (20 months old) control rats with those of rats exposed to transcranial near-infrared laser over 58 consecutive days. Statistical analyses of the brain metabolomics data indicated that chronic transcranial photobiomodulation (1) significantly enhances the metabolic pathways of young rats, particularly for excitatory neurotransmission and oxidative metabolism, and (2) restores the altered metabolic pathways of aged rats towards levels found in younger rats, mainly in the cerebral cortex. These novel metabolomics findings may help complement other laser-induced neurocognitive, neuroprotective, anti-inflammatory, and antioxidant effects described in the literature.