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.

The role of gut-brain axis in a rotenone-induced rat model of Parkinson's disease.

Parkinson's disease (PD) is a widespread neurodegenerative condition affecting millions globally. This investigation centered on the gut-brain axis in a rotenone-induced PD rat model. Researchers monitored behavioral shifts, histological modifications, neurodegeneration, and inflammation markers throughout the rats' bodies. Results revealed that rotenone-treated rats displayed reduced exploration (p = 0.004) and motor coordination (p < 0.001), accompanied by decreased Nissl staining and increased alpha-synuclein immunoreactivity in the striatum (p = 0.009). Additionally, these rats exhibited weight loss (T3, mean = 291.9 ± 23.67; T19, mean = 317.5 ± 17.53; p < 0.05) and substantial intestinal histological alterations, such as shortened villi, crypt architecture loss, and inflammation. In various regions, researchers noted elevated immunoreactivity to ionized binding adapter molecule (IBA)-1 (p < 0.05) and reduced immunoreactivity to glial fibrillary acidic protein (p < 0.05) and S100B (p < 0.001), indicating altered glial cell activity. Overall, these findings imply that PD is influenced by gut-brain axis changes and may originate in the intestine, impacting bidirectional gut-brain communication.

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.

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 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.

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.

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.

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.

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.

Therapeutic Potential of Photobiomodulation In Alzheimer's Disease: A Systematic Review.

Introduction: Alzheimer disease (AD) is characterized by the decline of cognitive functions such as learning and memory. Scientific society has proposed some non-pharmacological interventions, among which photobiomodulation has gained prominence for its beneficial effects. Therefore, we investigated, through systematic review, the therapeutic potential of photobiomodulation in AD. Methods: This systematic review was registered under the number CRD42019128416 in the International Prospective Record of Systematic Reviews (PROSPERO). A systematic search was conducted on the bibliographic databases (PubMed and ScienceDirect) with the keywords based on MeSH terms: "photobiomodulation therapy" or "low-level laser therapy" or "LLLT" or "light emitting diode" and "amyloid" or "Alzheimer". The data search was conducted from 2008 to 2019. We follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The search strategy included experimental in vivo and in vitro studies in the English language and photobiomodulation as a non-pharmacological intervention. We included 10 studies, being 5 in vivo studies, 4 in vitro studies and 1 study using in vivo and in vitro. To evaluate the quality of the studies, we used the Rob tool of the Systematic Review Center for Laboratory Animal Experimentation (SYRLE). Results: The studies showed that photobiomodulation is able to reduce inflammatory response, oxidative stress and apoptotic effects generated by amyloid beta (Aß) and restore mitochondrial function and cognitive behavior. Conclusion: Taken together, these results indicate that photobiomodulation may be a useful tool for treating AD.

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.

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 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.