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Neurodegenerative diseases (NDs) represent an unsolved problem to date with an ever-increasing population incidence. Particularly, Alzheimer's disease (AD) is the most widespread ND characterized by an accumulation of amyloid aggregates of beta-amyloid (Aß) and Tau proteins that lead to neuronal death and subsequent cognitive decline. Although neuroimaging techniques are needed to diagnose AD, the investigation of biomarkers within body fluids could provide important information on neurodegeneration. Indeed, as there is no definitive solution for AD, the monitoring of these biomarkers is of strategic importance as they are useful for both diagnosing AD and assessing the progression of the neurodegenerative state. In this context, exercise is known to be an effective non-pharmacological management strategy for AD that can counteract cognitive decline and neurodegeneration. However, investigation of the concentration of fluid biomarkers in AD patients undergoing exercise protocols has led to unclear and often conflicting results, suggesting the need to clarify the role of exercise in modulating fluid biomarkers in AD. Therefore, this critical literature review aims to gather evidence on the main fluid biomarkers of AD and the modulatory effects of exercise to clarify the efficacy and usefulness of this non-pharmacological strategy in counteracting neurodegeneration in AD.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Biomarcadores , Exercício Físico , Proteínas tau , Doença de Alzheimer/metabolismo , Doença de Alzheimer/terapia , Humanos , Biomarcadores/metabolismo , Exercício Físico/fisiologia , Peptídeos beta-Amiloides/metabolismo , Proteínas tau/metabolismo , Terapia por Exercício/métodosRESUMO
Neuronal death could be responsible for the cognitive impairments found in astronauts exposed to spaceflight, highlighting the need to identify potential countermeasures to ensure neuronal health in microgravity conditions. Therefore, differentiated HT22 cells were exposed to simulated microgravity by random positioning machine (RPM) for 48 h, treating them with a single administration of Trolox, recombinant irisin (r-Irisin) or both. Particularly, we investigated cell viability by MTS assay, Trypan Blue staining and western blotting analysis for Akt and B-cell lymphoma 2 (Bcl-2), the intracellular increase of reactive oxygen species (ROS) by fluorescent probe and NADPH oxidase 4 (NOX4) expression, as well as the expression of brain-derived neurotrophic factor (BDNF), a major neurotrophin responsible for neurogenesis and synaptic plasticity. Although both Trolox and r-Irisin manifested a protective effect on neuronal health, the combined treatment produced the best results, with significant improvement in all parameters examined. In conclusion, further studies are needed to evaluate the potential of such combination treatment in counteracting weightlessness-induced neuronal death, as well as to identify other potential strategies to safeguard the health of astronauts exposed to spaceflight.
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Cromanos , Fibronectinas , Ausência de Peso , Fibronectinas/farmacologia , Fibronectinas/metabolismo , Neurônios/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Diferenciação CelularRESUMO
Space colonization represents the most insidious challenge for mankind, as numerous obstacles affect the success of space missions. Specifically, the absence of gravitational forces leads to systemic physiological alterations, with particular emphasis on the musculoskeletal system. Indeed, astronauts exposed to spaceflight are known to report a significant impairment of bone microarchitecture and muscle mass, conditions clinically defined as osteoporosis and sarcopenia. In this context, space medicine assumes a crucial position, as the development of strategies to prevent and/or counteract weightlessness-induced alterations appears to be necessary. Furthermore, the opportunity to study the biological effects induced by weightlessness could provide valuable information regarding adaptations to spaceflight and suggest potential treatments that can preserve musculoskeletal health under microgravity conditions. Noteworthy, improving knowledge about the latest scientific findings in this field of research is crucial, as is thoroughly investigating the mechanisms underlying biological adaptations to microgravity and searching for innovative solutions to counter spaceflight-induced damage. Therefore, this narrative study review, performed using the MEDLINE and Google Scholar databases, aims to summarize the most recent evidence regarding the effects of real and simulated microgravity on the musculoskeletal system and to discuss the effectiveness of the main defence strategies used in both real and experimental settings.
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Osteosarcopenia (OSP) is a geriatric syndrome characterized by the coexistence of osteoporosis and sarcopenia and associated with an increased risk of fragility fractures, disability, and mortality. For patients with this syndrome, musculoskeletal pain represents the most significant challenge since, in addition to limiting the individual's functionality and promoting disability, it has a huge psychological burden involving anxiety, depression, and social withdrawal. Unfortunately, the molecular mechanisms involved in the development and persistence of pain in OSP have not yet been fully elucidated, although immune cells are known to play a key role in these processes. Indeed, they release several molecules that promote persistent inflammation and nociceptive stimulation, resulting in the gating of ion channels responsible for the generation and propagation of the noxious stimulus. The adoption of countermeasures to counteract the OSP progression and reduce the algic component appears to be necessary, providing patients with a better quality of life and greater adherence to treatment. In addition, the development of multimodal therapies, based on an interdisciplinary approach, appears to be crucial, combining the use of anti-osteoporotic drugs with an educational programme, regular physical activity, and proper nutrition to eliminate risk factors. Based on this evidence, we conducted a narrative review using the PubMed and Google Scholar search engines to summarize the current knowledge on the molecular mechanisms involved in the pain development in OSP and the potential countermeasures to be taken. The lack of studies addressing this topic highlights the need to conduct new research into the resolution of an ever-expanding social problem.
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Spaceflight exposure, like prolonged skeletal unloading, is known to result in significant bone loss, but the molecular mechanisms responsible are still partly unknown. This impairment, characterizing both conditions, suggests the possibility of identifying common signalling pathways and developing innovative treatment strategies to counteract the bone loss typical of astronauts and osteoporotic patients. In this context, primary cell cultures of human osteoblasts derived from healthy subjects and osteoporotic patients were exposed to random positioning machine (RPM) to reproduce the absence of gravity and to exacerbate the pathological condition, respectively. The duration of exposure to RPM was 3 or 6 days, with the aim of determining whether a single administration of recombinant irisin (r-irisin) could prevent cell death and mineralizing capacity loss. In detail, cellular responses were assessed both in terms of death/survival, by MTS assay, analysis of oxidative stress and caspase activity, as well as the expression of survival and cell death proteins, and in terms of mineralizing capacity, by investigating the pentraxin 3 (PTX3) expression. Our results suggest that the effects of a single dose of r-irisin are maintained for a limited time, as demonstrated by complete protection after 3 days of RPM exposure and only partial protection when RPM exposure was for a longer time. Therefore, the use of r-irisin could be a valid strategy to counteract the bone mass loss induced by weightlessness and osteoporosis. Further studies are needed to determine an optimal treatment strategy based on the use of r-irisin that is fully protective even over very long periods of exposure and/or to identify further approaches to be used in a complementary manner.
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BACKGROUND: Long-term detraining consists of a physiological partial or total reduction of the adaptations induced by training caused by a suspension period of the training itself longer than 4 weeks. The aim of this study was to analyze a group of young soccer players by assessing the effects of long-term detraining on neuromuscular performance. METHODS: A study sample of 35 young soccer players of subelite level (age: 14.5±0.5 years) was recruited. The subjects were tested 7 days before the interruption of training for the summer break (T0), and at the end of the 7-week detraining period (T1). RESULTS: No statistically significant differences were found for BMI (P=0.283) and percentage of fat mass (P=0.273) between T0 and T1. PUSH UP (P=0.016; ES [effect size]=0.2) and SIT UP (P=0.001; ES=1.2) test values show statistically significant increase, those of CHIN UP (P=0.05; ES=-0.2), instead, a statistically significant worsening. Statistically significant but moderate differences on speed running test 30 meters (P=0.001; ES=0.3) are observed as well as trivial differences on 50 meters (P=0.001; ES=0.2), while differences on 10, 15 and 20 meters are irrelevant. As for the jump tests, values show a slight worsening (P=0.135; ES=0.2) in Squat Jump and Counter Movement Jump (P=0.153; ES=0.2) without statistical significance. CONCLUSIONS: A 7-week-long detraining period does not seem to produce any appreciable changes on neuromuscular performance of the lower limb (trained muscle) in young soccer players. As regards the analyzed age group, coaches should not focus their attention on neuromuscular efficiency maintenance exercises in the off-season period.
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Desempenho Atlético , Corrida , Futebol , Humanos , Adolescente , Futebol/fisiologia , Corrida/fisiologia , Exercício Físico , Músculos , Movimento , Desempenho Atlético/fisiologiaRESUMO
BACKGROUND: To verify the effects in terms of feasibility, strength and functional abilities of a standardized exercise training method that is partially supported (home training), with the aim of improving motor abilities and well-being. METHODS: A total of 67 participants underwent two sessions per week for 12 weeks for the program, based on 8 sequences with specific body part targets, with each sequence made up of 9 exercises. OUTCOME MEASURES: Recording of training session data, Chair Test, Hand Grip Test, Timed Up-and-Go Test, Stork Balance Test, Sit-and-Reach Test, VAS, Perceived Physical Exertion. RESULTS: In total, 97% of the sample were "adherent" (more than 70% of the prescribed treatments performed). The rate of adverse events was infrequent (only 8). Chair Test +31%, Hand Grip Test +6%, Timed Up-and-Go Test -17%, Stork Balance Test +65%, Sit-and-Reach Test +55%, VAS -34%, Perceived Physical Exertion -69%. CONCLUSIONS: Home training has good feasibility (adherence, tolerability, safety) and cost-effectiveness ratio and improves both strength and functional abilities, which, in turns, helps to improve motor abilities and well-being.
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Several studies agree that mechanical vibration can induce physiological changes at different levels, improving neuromuscular function through postural control strategies, muscle tuning mechanisms and tonic vibration reflexes. Whole-body vibration has also been reported to increase bone mineral density and muscle mass and strength, as well as to relieve pain and modulate proprioceptive function in patients with osteoarthritis or lower back pain. Furthermore, vibratory training was found to be an effective strategy for improving the physical performance of healthy athletes in terms of muscle strength, agility, flexibility, and vertical jump height. Notably, several benefits have also been observed at the brain level, proving to be an important factor in protecting and/or preventing the development of age-related cognitive disorders. Although research in this field is still debated, certain molecular mechanisms responsible for the response to whole-body vibration also appear to be involved in physiological adaptations to exercise, suggesting the possibility of using it as an alternative or reinforcing strategy to canonical training. Understanding these mechanisms is crucial for the development of whole body vibration protocols appropriately designed based on individual needs to optimize these effects. Therefore, we performed a narrative review of the literature, consulting the bibliographic databases MEDLINE and Google Scholar, to i) summarize the most recent scientific evidence on the effects of whole-body vibration and the molecular mechanisms proposed so far to provide a useful state of the art and ii) assess the potential of whole-body vibration as a form of passive training in place of or in association with exercise.
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Whole body vibration (WBV) is well known to exert beneficial effects on multiple tissues, improving synaptic transmission, muscle mass, bone quality, and reducing anxiety and depressive behavior. However, the underlying molecular mechanisms are not yet fully understood, and organs and tissues may respond differently to the vibratory stimulus depending on multiple factors. Therefore, we investigated the WBV effects on the brain and musculoskeletal tissue of 4-month-old young mice, evaluating synaptic plasticity by electrophysiological recordings and tissue organization by histology and histomorphometric analysis. Specifically, WBV protocols were characterized by the same vibration frequency (45 Hz), but different in vibration exposure time (five series of 3 min for the B protocol and three series of 2 min and 30 s for the C protocol) and recovery time between two vibration sessions (1 min for the B protocol and 2 min and 30 s for the C protocol). In addition, immunohistochemistry was conducted to evaluate the expression of fibronectin type III domain-containing protein 5 (FNDC5), as well as that of tissue-specific markers, such as brain-derived neurotrophic factor (BDNF) in brain, myostatin in muscle and collagen I (COL-1) in bone. Our results suggest that the WBV effects depend closely on the type of protocol used and support the hypothesis that different organs or tissues have different susceptibility to vibration. Further studies will be needed to deepen our knowledge of physiological adaptations to vibration and develop customized WBV protocols to improve and preserve cognitive and motor functions.
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Fator Neurotrófico Derivado do Encéfalo , Vibração , Adaptação Fisiológica , Animais , Encéfalo , Colágeno , Fibronectinas , Camundongos , Miostatina , Vibração/uso terapêuticoRESUMO
BACKGROUND: In water polo, more physical and performance variables are related to a performance in a match. The aim of our work was therefore: (a) to evaluate the relationships between anthropometric characteristics and performance tests and performance in a match in young male water polo players; (b) to propose new guidelines for match analysis. METHODS: Multiple regression analysis was used to study the results in anthropometric evaluations (height, body mass, chest circumference, arm span, non-dominant arm length) and performance tests (push-up, chin-up, shuttle swim test, sprint swim 10 m, eggbeater kick, 100 m swimming) and two coaches' evaluations of two friendly matches using new guidelines. A total of 130 subjects (age: 15.6 ± 0.9 years) were involved in the study. RESULTS: In this study, we proposed a new performance model based on multiple regression analysis (r = 0.85, r2 = 0.73, adjusted r2 = 0.57) and described by the following equation: Coach's Evaluation = 151.6 + (-0.016 × height) + (0.6 × body mass) + (-0.82 × chest) + (-0.59 × arm span) + (0.75 × non dominant arm length) + (-0.037 × push up) + (0.17 × chin up) + (5.87 × shuttle swim test) + (-2.2 × 10 m sprint swim) + (0.05 × eggbeater kick) + (-0.35 × 100 m swimming). Inter-observer values were: CV: -3.9%, ICC: 0.82, ES: 0.1. Intra-observer: CV: -4.1%, ICC: 0.96, ES: 0.06. CONCLUSIONS: The relationships between anthropometric and performance variables and the match analysis have been statistically described. The equation found can be used to predict the overall performance of a player and permits evaluations of how much the improvement in one of the qualities can affect the players' overall performance. Moreover, the new method for match analysis we have proposed showed a good reliability and can be used for new studies on water polo.
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Desempenho Atlético , Esportes Aquáticos , Adolescente , Humanos , Masculino , Análise de Regressão , Reprodutibilidade dos Testes , NataçãoRESUMO
Scientific evidence has demonstrated the power of physical exercise in the prevention and treatment of numerous chronic and/or age-related diseases, such as musculoskeletal, metabolic, and cardiovascular disorders. In addition, regular exercise is known to play a key role in the context of neurodegenerative diseases, as it helps to reduce the risk of their onset and counteracts their progression. However, the underlying molecular mechanisms have not yet been fully elucidated. In this regard, neurotrophins, such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glia cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), have been suggested as key mediators of brain health benefits, as they are involved in neurogenesis, neuronal survival, and synaptic plasticity. The production of these neurotrophic factors, known to be increased by physical exercise, is downregulated in neurodegenerative disorders, suggesting their fundamental importance in maintaining brain health. However, the mechanism by which physical exercise promotes the production of neurotrophins remains to be understood, posing limits on their use for the development of potential therapeutic strategies for the treatment of neurodegenerative diseases. In this literature review, we analyzed the most recent evidence regarding the relationship between physical exercise, neurotrophins, and brain health, providing an overview of their involvement in the onset and progression of neurodegeneration.
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Musculoskeletal pain is a condition that characterises several diseases and represents a constantly growing issue with enormous socio-economic burdens, highlighting the importance of developing treatment algorithms appropriate to the patient's needs and effective management strategies. Indeed, the algic condition must be assessed and treated independently of the underlying pathological process since it has an extremely negative impact on the emotional and psychic aspects of the individual, leading to isolation and depression. A full understanding of the pathophysiological mechanisms involved in nociceptive stimulation and central sensitization is an important step in improving approaches to musculoskeletal pain. In this context, the bidirectional relationship between immune cells and neurons involved in nociception could represent a key point in the understanding of these mechanisms. Therefore, we provide an updated overview of the magnitude of the musculoskeletal pain problem, in terms of prevalence and costs, and summarise the role of the most important molecular players involved in the development and maintenance of pain. Finally, based on the pathophysiological mechanisms, we propose a model, called the "musculoskeletal pain cycle", which could be a useful tool to counteract resignation to the algic condition and provide a starting point for developing a treatment algorithm for the patient with musculoskeletal pain.
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Bone loss is among the most frequent changes seen in astronauts during space missions. Although weightlessness is known to cause high bone resorption and a rapid decrease in bone minerals and calcium, the underlying mechanisms are not yet fully understood. In our work, we investigated the influence of random positioning machine (RPM) exposure on the mineralization process in the SAOS-2 cell line, in osteogenic and non-osteogenic conditions, by examining changes in their mineralizing capacity and in the expression of PTX3, a positive regulator of bone mineralization. We analyzed cell viability by MTS assay and the mineralization process after staining with Toluidine Blue and Alizarin Red, while PTX3 expression was investigated by immunocytochemistry and western blotting analysis. Our results showed that RPM exposure increased cells' viability and improved their mineralizing competence when not treated with osteogenic cocktail. In contrast, in osteogenic conditions, cells exposed to RPM showed a reduction in the presence of calcification-like structures, mineral deposits and PTX3 expression, suggesting that the effects of RPM exposure on mineralizing matrix deposition depend on the presence of osteogenic factors in the culture medium. Further studies will be needed to clarify the role of potential mineralization markers in the cellular response to the simulated biological effects of microgravity, paving the way for a new approach to treating osteoporosis in astronauts exposed to spaceflight.
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Several scientific evidence have shown that exposure to microgravity has a significant impact on the health of the musculoskeletal system by altering the expression of proteins and molecules involved in bone-muscle crosstalk, which is also observed in the research of microgravity effect simulation. Among these, the expression pattern of myostatin appears to play a key role in both load-free muscle damage and the progression of age-related musculoskeletal disorders, such as osteoporosis and sarcopenia. Based on this evidence, we here investigated the efficacy of treatment with anti-myostatin (anti-MSTN) antibodies on primary cultures of human satellite cells exposed to 72 h of random positioning machine (RPM). Cell cultures were obtained from muscle biopsies taken from a total of 30 patients (controls, osteoarthritic, and osteoporotic) during hip arthroplasty. The Pax7 expression by immunofluorescence was carried out for the characterization of satellite cells. We then performed morphological evaluation by light microscopy and immunocytochemical analysis to assess myostatin expression. Our results showed that prolonged RPM exposure not only caused satellite cell death, but also induced changes in myostatin expression levels with group-dependent variations. Surprisingly, we observed that the use of anti-MSTN antibodies induced a significant increase in cell survival after RPM exposure under all experimental conditions. Noteworthy, we found that the negative effect of RPM exposure was counteracted by treatment with anti-MSTN antibodies, which allowed the formation of numerous myotubes. Our results highlight the role of myostatin as a major effector of the cellular degeneration observed with RPM exposure, suggesting it as a potential therapeutic target to slow the muscle mass loss that occurs in the absence of loading.
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Here we proposed the most recent innovations in the use of Breast Specific Gamma Imaging with 99mTc-sestamibi for the management of breast cancer patients. To this end, we reported the recent discoveries concerning: a) the implementation of both instrumental devices and software, b) the biological mechanisms involved in the 99mTc-sestamibi uptake in breast cancer cells, c) the evaluation of Breast Specific Gamma Imaging with 99mTc-sestamibi as predictive markers of metastatic diseases. In this last case, we also reported preliminary data about the capability of Breast Specific Gamma Imaging with 99mTc-sestamibi to identify breast cancer lesions with high propensity to form bone metastatic lesions due to the presence of Breast Osteoblast-Like Cells.
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Neoplasias da Mama , Tecnécio Tc 99m Sestamibi , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Feminino , Humanos , Cintilografia , Compostos RadiofarmacêuticosRESUMO
BACKGROUND: We intended to verify through time-motion analysis the characteristics of the sequences of actions in terms of occurrence during water polo matches: number, duration, and possible relationships with technical-tactical aspects. METHODS: Water polo matches played at the 18th FINA World Championships 2019, Gwangju, South Korea, were chosen for examination, and the analysis involved both single actions and Trains of Actions (ToAs). A ToA is a sequence of actions that occurs during the match without actual game interruption. RESULTS: A total of 1261 game actions were evaluated in the 17 matches analyzed. In 89% of cases the actions occurred in ToAs while in 11% of cases they took place as single actions. On average, each match included 74.4±5.3 actions; of these, only 7.9±3.4 (CI at 95%: lower bound 6.1 and upper bound 9.6) were single actions while 66.2±5.5 occurred in sequences (ToA2=29.6±9.0%; ToA3=26.1±9.7%; ToA4=16.5±10.6%). The winning team performed on average more actions than the losing one (42.1±6.1 vs. 32.0±6.4; effect size: 1.67; P value: 0.001). The ToAs had different compositions, from 2 to 18 actions, and then very different durations, from about 1 minute up to 8 minutes. 66% of goals were scored after ToAs and 34% after single actions. CONCLUSIONS: The study of ToAs provides useful information on the physiological demand of the game, which may help to plan and organize physical training making it as specific as possible. The description of ToAs can help coaches to better define the game scenario and understand which technical and tactical measures are needed to improve game organization.
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Desempenho Atlético , Esportes Aquáticos , Desempenho Atlético/fisiologia , Exercício Físico , Humanos , Masculino , República da CoreiaRESUMO
Aerobic training is known to influence cognitive processes, such as memory and learning, both in animal models and in humans. Particularly, in vitro and in vivo studies have shown that aerobic exercise can increase neurogenesis in the dentate gyrus, improve hippocampal long-term potentiation (LTP), and reduce age-related decline in mnemonic function. However, the underlying mechanisms are not yet fully understood. Based on this evidence, the aim of our study was to verify whether the application of two aerobic training protocols, different in terms of speed and speed variation, could modulate synaptic plasticity in a young murine model. Therefore, we assessed the presence of any functional changes by extracellular recordings in vitro in mouse hippocampal slices and structural alterations by transmission electron microscopy (TEM). Our results showed that an aerobic training protocol, well designed in terms of speed and speed variation, significantly contributes to improving synaptic plasticity and hippocampal ultrastructure, optimizing its benefits in the brain. Future studies will aim to clarify the underlying biological mechanisms involved in the modulation of synaptic plasticity induced by aerobic training.
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Niemann-Pick type C (NPC) disease is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol in the late endo-lysosomal system of cells. Progressive neurological deterioration and the onset of symptoms, such as ataxia, seizures, cognitive decline, and severe dementia, are pathognomonic features of the disease. In addition, different pathological similarities, including degeneration of hippocampal and cortical neurons, hyperphosphorylated tau, and neurofibrillary tangle formation, have been identified between NPC disease and other neurodegenerative pathologies. However, the underlying pathophysiological mechanisms are not yet well understood, and even a real cure to counteract neurodegeneration has not been identified. Therefore, the combination of current pharmacological therapies, represented by miglustat and cyclodextrin, and non-pharmacological approaches, such as physical exercise and appropriate diet, could represent a strategy to improve the quality of life of NPC patients. Based on this evidence, in our review we focused on the neurodegenerative aspects of NPC disease, summarizing the current knowledge on the molecular and biochemical mechanisms responsible for cognitive impairment, and suggesting physical exercise and nutritional treatments as additional non-pharmacologic approaches to reduce the progression and neurodegenerative course of NPC disease.
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Suscetibilidade a Doenças , Degeneração Neural/etiologia , Doença de Niemann-Pick Tipo C/etiologia , Doença de Niemann-Pick Tipo C/terapia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Tomada de Decisão Clínica , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Gerenciamento Clínico , Humanos , Degeneração Neural/diagnóstico , Doença de Niemann-Pick Tipo C/diagnóstico , Doença de Niemann-Pick Tipo C/tratamento farmacológico , Resultado do TratamentoRESUMO
Bone and muscle tissues influence each other through the integration of mechanical and biochemical signals, giving rise to bone-muscle crosstalk. They are also known to secrete osteokines, myokines, and cytokines into the circulation, influencing the biological and pathological activities in local and distant organs and cells. In this regard, even osteoporosis and sarcopenia, which were initially thought to be two independent diseases, have recently been defined under the term "osteosarcopenia", to indicate a synergistic condition of low bone mass with muscle atrophy and hypofunction. Undoubtedly, osteosarcopenia is a major public health concern, being associated with high rates of morbidity and mortality. The best current defence against osteosarcopenia is prevention based on a healthy lifestyle and regular exercise. The most appropriate type, intensity, duration, and frequency of exercise to positively influence osteosarcopenia are not yet known. However, combined programmes of progressive resistance exercises, weight-bearing impact exercises, and challenging balance/mobility activities currently appear to be the most effective in optimising musculoskeletal health and function. Based on this evidence, the aim of our review was to summarize the current knowledge about the role of exercise in bone-muscle crosstalk, highlighting how it may represent an effective alternative strategy to prevent and/or counteract the onset of osteosarcopenia.
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Aerobic exercise (AE) is known to produce beneficial effects on brain health by improving plasticity, connectivity, and cognitive functions, but the underlying molecular mechanisms are still limited. Neurexins (Nrxns) are a family of presynaptic cell adhesion molecules that are important in synapsis formation and maturation. In vertebrates, three-neurexin genes (NRXN1, NRXN2, and NRXN3) have been identified, each encoding for α and ß neurexins, from two independent promoters. Moreover, each Nrxns gene (1-3) has several alternative exons and produces many splice variants that bind to a large variety of postsynaptic ligands, playing a role in trans-synaptic specification, strength, and plasticity. In this study, we investigated the impact of a continuous progressive (CP) AE program on alternative splicing (AS) of Nrxns on two brain regions: frontal cortex (FC) and hippocampus. We showed that exercise promoted Nrxns1-3 AS at splice site 4 (SS4) both in α and ß isoforms, inducing a switch from exon-excluded isoforms (SS4-) to exon-included isoforms (SS4+) in FC but not in hippocampus. Additionally, we showed that the same AE program enhanced the expression level of other genes correlated with synaptic function and plasticity only in FC. Altogether, our findings demonstrated the positive effect of CP AE on FC in inducing molecular changes underlying synaptic plasticity and suggested that FC is possibly a more sensitive structure than hippocampus to show molecular changes.