Physical exercise and health: a focus on its protective role in neurodegenerative diseases

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 neurotrophin4 (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

Dose–Response Effect of Vibratory Stimulus on Synaptic and Muscle Plasticity in a Middle-Aged Murine Model

Whole body vibration plays a central role in many work categories and can represent a health risk to the musculoskeletal system and peripheral nervous system. However, studies in animal and human models have shown that vibratory training, experimentally and/or therapeutically induced, can exert beneficial effects on the whole body, as well as improve brain functioning and reduce cognitive decline related to the aging process. Since the effects of vibratory training depend on several factors, such as vibration frequency and vibration exposure time, in this work, we investigated whether the application of three different vibratory protocols could modulate synaptic and muscle plasticity in a middle-aged murine model, counteracting the onset of early symptoms linked to the aging process. To this end, we performed in vitro electrophysiological recordings of the field potential in the CA1 region of mouse hippocampal slices, as well as histomorphometric and ultrastructural analysis of muscle tissue by optic and transmission electron microscopy, respectively. Our results showed that protocols characterized by a low vibration frequency and/or a longer recovery time exert positive effects at both hippocampal and muscular level, and that these effects improve significantly by varying both parameters, with an action comparable with a dose–response effect. Thus, we suggested that vibratory training may be an effective strategy to counteract cognitive impairment, which is already present in the early stages of the aging process, and the onset of sarcopenia, which is closely related to a sedentary lifestyle. Future studies are needed to understand the underlying molecular mechanisms and to determine an optimal vibratory training protocol

Effects of short-term aerobic exercise in a mouse model of Niemann-Pick type C Disease on synaptic and muscle plasticity

Background. Physical exercise can reduce the risk of developing chronic diseases andslow the onset of neurodegenerative diseases. Since it has not been assessed which kindof training protocol might positively modulate both synaptic and muscular plasticity inneurodegenerative diseases, we studied in a mouse model of Niemann Pick type C disease,a model of minimal Alzheimer’s Disease, the effect of a short term protocol.Methods. We evaluated the effect of a short term, aerobic uniform exercise training onsynaptic and muscle plasticity in three different mice groups: WT controls, NPC1+/-and NPC1-/- animals. The results were compared with those obtained in the sedentaryrespective groups. We analyzed the effects on synaptic plasticity by in vitro extracellularrecordings in hippocampal mouse slices; moreover hippocampal and muscle tissuemorphological structure have been investigated by transmission electron microscopy, tohighlight any structural and functional changes due to training.Results. The results indicate a rescue of long-term potentiation in homozygous but notin heterozygous mice slices and an induction of neuronal plasticity, observed by morphologicalanalysis, both in homozygous and in heterozygous trained mice.Conclusions. Hence this protocol is adequate to improve long term potent

Effects of Different Continuous Aerobic Training Protocols in a Heterozygous Mouse Model of Niemann-Pick Type C Disease

The positive effects of physical activity on cognitive functions are widely known. Aerobic training is known to promote the expression of neurotrophins, thus inducing an increase in the development and survival of neurons, as well as enhancing synaptic plasticity. Based on this evidence, in the present study, we analyze the effects of two different types of aerobic training, progressive continuous (PC) and varying continuous (VC), on synaptic and muscular plasticity in heterozygous mice carrying the genetic mutation for Niemann-Pick type C disease. We also analyze the effects on synaptic plasticity by extracellular recordings in vitro in mouse hippocampal slices, while the morphological structure of muscle tissue was studied by transmission electron microscopy. Our results show a modulation of synaptic plasticity that varies according to the type of training protocol used, and only the VC protocol administered twice a week, has a significantly positive effect on long-term potentiation. On the contrary, ultrastructural analysis of muscle tissue shows an improvement in cellular conditions in all trained mice. These results confirm the beneficial effects of exercise on quality of life, supporting the hypothesis that physical activity could represent an alternative therapeutic strategy for patients with Niemann-Pick type C disease

The Nutraceutical Dehydrozingerone and Its Dimer Counteract Inflammation- and Oxidative Stress-Induced Dysfunction of In Vitro

Atherosclerosis is characterized by endothelial dysfunction, mainly induced by inflammation and oxidative stress. Increased reactive oxygen species (ROS) production together with increased adhesion molecules and thrombogenic tissue factor (TF) expression on endothelial cells has a key role in proatherogenic mechanisms. Therefore downmodulation of these molecules could be useful for reducing the severity of inflammation and atherosclerosis progression. Dehydrozingerone (DHZ) is a nutraceutical compound with anti-inflammatory and antioxidant activities. In this study we evaluated the ability of DHZ and its symmetric dimer to modulate hydrogen peroxide- (H2O2-) induced ROS production in human umbilical vein endothelial cells (HUVEC). We also evaluated intercellular adhesion molecule- (ICAM-) 1, vascular cell adhesion molecule- (VCAM-) 1, and TF expression in HUVEC activated by tumor necrosis factor- (TNF-) α. HUVEC pretreatment with DHZ and DHZ dimer reduced H2O2-induced ROS production and inhibited adhesion molecule expression and secretion. Of note, only DHZ dimer was able to reduce TF expression. DHZ effects were in part mediated by the inhibition of the nuclear factor- (NF-) κB activation. Overall, our findings demonstrate that the DHZ dimer exerts a potent anti-inflammatory, antioxidant, and antithrombotic activity on endothelial cells and suggest potential usefulness of this compound to contrast the pathogenic mechanisms involved in atherosclerosis progression

Intermittent fasting applied in combination with rotenone treatment exacerbates dopamine neurons degeneration in mice

Intermittent fasting (IF) was suggested to be a powerful nutritional strategy to prevent the onset of age-related neurodegenerative diseases associated with compromised brain bioenergetics. Whether the application of IF in combination with a mitochondrial insult could buffer the neurodegenerative process has never been explored yet. Herein, we defined the effects of IF in C57BL/6J mice treated once per 24 h with rotenone (Rot) for 28 days. Rot is a neurotoxin that inhibits the mitochondrial complex I and causes dopamine neurons degeneration, thus reproducing the neurodegenerative process observed in Parkinson\u2019s disease (PD). IF (24 h alternate-day fasting) was applied alone or in concomitance with Rot treatment (Rot/IF). IF and Rot/IF groups showed the same degree of weight loss when compared to control and Rot groups. An accelerating rotarod test revealed that only Rot/IF mice have a decreased ability to sustain the test at the higher speeds. Rot/IF group showed a more marked decrease of dopaminergic neurons and increase in alpha-synuclein (a-syn) accumulation with respect to Rot group in the substantia nigra (SN). Through lipidomics and metabolomics analyses, we found that in the SN of Rot/IF mice a significant elevation of excitatory amino acids, inflammatory lysophospholipids and sphingolipids occurred. Collectively, our data suggest that, when applied in combination with neurotoxin exposure, IF does not exert neuroprotective effects but rather exacerbate neuronal death by increasing the levels of excitatory amino acids and inflammatory lipids in association with altered brain membrane composition

A Study about a New Standardized Method of Home-Based Exercise in Elderly People Aged 65 and Older to Improve Motor Abilities and Well-Being: Feasibility, Functional Abilities and Strength Improvements

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

Modulation of Synaptic Plasticity by Vibratory Training in Young and Old Mice

In the past 40 years, scientific research has shown how Whole Body Vibration concept represents a strong stimulus for the whole organism. Low (<30 Hz), medium (30–80 Hz), and high (>80 Hz) frequency vibrations can have both positive and negative effects, depending on the oscillation type and duration of exposure to which the body is subjected. However, very little is known about the effects of vibratory training on the brain. In this regard, we verified whether three vibratory training protocols, differing in terms of vibration frequency and exposure time to vibration, could modulate synaptic plasticity in an experimental mouse model, by extracellular recordings in vitro in hippocampal slices of mice of 4 and 24 months old. Our results showed that vibratory training can modulate synaptic plasticity differently, depending on the protocol used, and that the best effects are related to the training protocol characterized by a low vibration frequency and a longer recovery time. Future studies will aim to understand the brain responses to various types of vibratory training and to explore the underlying mechanisms, also evaluating the presence of any structural and functional changes due to vibratory training

Whole Body Vibration: A Valid Alternative Strategy to Exercise?

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