Effects of Aerobic Exercise and Resistance Training on Cognitive Function: Comparative Study Based on FNDC5/Irisin/BDNF Pathway.

INTRODUCTION: Exercise has been recommended to suppress or prevent cognitive decline. Aerobic exercise (AE) may suppress cognitive decline via the fibronectin type III domain-containing protein 5 (FNDC5)/irisin/brain-derived neurotrophic factor (BDNF) pathway, and resistance training (RT) has a preventive effect on cognitive decline. However, the underlying mechanism remains unclear. This study verified the differences in the effects of AE and RT in suppressing and preventing cognitive decline based on the FNDC5/irisin/BDNF pathway. METHODS: We divided senescence-accelerated mouse-prone 8 into three groups: control (CON), AE, and RT and evaluated their memory during exercise intervention through a novel object recognition (NOR) task. We quantified FNDC5/irisin, mBDNF, and TrkB in the hippocampus using enzyme-linked immunosorbent assay and FNDC5 in skeletal muscle using Western blotting (WB). RESULTS: Behavioral analysis using NOR showed that values for both AE and RT were significantly greater than those for CON. WB analysis showed that the peripheral FNDC5 expression in the skeletal muscle was increased in AE. The expression levels of FNDC5/irisin and mBDNF in the hippocampus were significantly increased in both AE and RT compared with that in CON but that if TrkB was increased only in AE. CONCLUSION: No significant difference was observed between AE and RT in the inhibitory effect on age-related cognitive decline, and both groups were effective. The FNDC5/Irisin/BDNF pathway, which was the focus of this experiment, may be specific to AE. The mechanism that suppresses cognitive decline may differ depending on the type of exercise.

FNDC5/irisin mediates the protective effects of Innovative theta-shaking exercise on mouse memory.

As a passive motion and non-invasive treatment, theta-shaking exercise is considered an alternative to traditional active exercise for slowing down brain ageing. Here, we studied the influence of theta-shaking exercise on fibronectin type III domain containing 5/irisin (FNDC5/irisin) in the anterior nucleus of the thalamus, hippocampus, and medial prefrontal cortex (ATN-HPC-MPFC). Further, we assessed memory in senescence-accelerated prone mice (SAMP-10 mice) using a behavioural test to confirm the protective effect of theta-shaking exercise against age-related memory decline. SAMP-10 mice were subjected to theta-shaking exercise for 9-30 weeks. Mice then performed the T-maze test and passive avoidance task. Immunohistochemical analysis and ELISA were used to assess FNDC5/irisin, nerve growth factor (NGF), and neurotrophin 4/5 (NT4/5) expression in the ATN-HPC-MPFC. In the shaking group, FNDC5 was locally upregulated within the hippocampus and MPFC area rather than exhibiting even distribution throughout brain tissue. Irisin levels were generally higher in the control group. Meanwhile, hippocampal NGF levels were significantly higher in the shaking group, with no differences noted in neurotrophin levels. Theta-shaking preserved normal neurons in certain sub-regions. However, no beneficial changes in neuronal density were noted in the ATN. Theta-shaking exercise positively affects memory function in SAMP-10 mice. FNDC5 upregulation and higher levels of NGF, along with the potential involvement of irisin, may have contributed to the preservation of normal neuronal density in the hippocampus and MPFC subregions.

Effects of online frame-of-reference training on assessment accuracy in the objective structured clinical examination for physical therapy students.

Objectives: This study investigates how online frame-of-reference (FOR) training of raters of the objective structured clinical examination (OSCE) for physical therapy students affects assessment accuracy. Methods: The research was conducted in a 1-month-long randomized controlled trial. Participants: The participants were 36 physical therapists without experience assessing clinical skills using the OSCE. The training group completed the FOR training online, which was conducted once a week in two 90-minute sessions. The control group self-studied the rubric rating chart used in the assessment. As a measure of accuracy, weighted kappa coefficients were used to check the agreement between correct score and those assessment by the participant in the OSCE. Results: The scores of the training group were higher than those of the control group in both post- and follow-up assessments, showing significant differences. No significant difference was found based on the assessment time and group for the high-agreement groups. Furthermore, scores of the low-accuracy training group were higher in the post- and follow-up assessments than those in the pre-assessment, showing significant differences. Conclusions: Online FOR training of the raters of the OSCE for physical therapists improved the assessment accuracy of the raters who had low accuracy in the pre-assessment; this improvement was maintained.

Facilitation of imitative movement in patients with chronic hemiplegia triggered by illusory ownership.

The sense of body ownership, the feeling that one's body belongs to oneself, is a crucial subjective conscious experience of one's body. Recent methodological advances regarding crossmodal illusions have provided novel insights into how multisensory interactions shape human perception and cognition, underpinning conscious experience, particularly alteration of body ownership. Moreover, in post-stroke rehabilitation, encouraging the use of the paretic limb in daily life is considered vital, as a settled sense of ownership and attentional engagement toward the paralyzed body part may promote increased frequency of its use and prevent learned nonuse. Therefore, in addition to traditional methods, novel interventions using neurorehabilitation techniques that induce self-body recognition are needed. This study investigated whether the illusory experience of a patient's ownership alterations of their paretic hand facilitates the enhancement in the range of motion of succeeding imitation movements. An experiment combining a modified version of the rubber hand illusion with imitation training was conducted with chronic hemiplegia. A larger imitation movement of the paretic hand was observed in the illusion-induced condition, indicating that the feeling of ownership toward the observed limb promotes the induction of intrinsic potential for motor performance. This training, using subjective experience, may help develop new post-stroke rehabilitation interventions.

Review of the health-promoting effects of exercise and the involvement of myokines.

Exercise reduces the risk of obesity-based, lifestyle-related diseases, such as metabolic abnormalities and cardiovascular diseases. The present review covers the health-promoting effects of exercise from the point of view of the physiologically active factor myokine, which is secreted by skeletal muscle, and focuses on the skeletal muscle as a new endocrine organ. Myokines have various effects, such as preventing metabolic syndrome by breaking down fat, preventing diabetes by improving glucose metabolism, and preventing progression of arteriosclerosis, dementia, and osteoporosis by enhancing bone metabolism. These substances also stabilize blood pressure, prevent cancer, increase immunity against infections, and prevent the development of age-associated diseases. Myokines are secreted by skeletal muscle into blood vessels, allowing them to exert systemic endocrine effects in organs throughout the body. Myokines are involved in bodily homeostasis and adaptation to the environment, and function by a mechanism similar to that of the skeletal muscle mass regulatory mechanism. Determining the relationships between multiple organs and their biological significance is important for exercise and health research. Progress in this field is expected to result in the identification of pathological mechanisms of action, development of new drugs, evaluation of the effectiveness of biomarkers over a wide range, and future improvement in healthcare.

Exercise through Shaking Stimuli Suppresses Cancer Growth via the Wnt pathway in ApcMin/+ Mice.

OBJECTIVE: Exercise has been reported to suppress colorectal cancer; however, the mechanism of suppression by exercise and its effect on the Wnt pathway, which is particularly involved in the early stage of carcinogenesis, remain unclear. In this study, we subjected ApcMin/+ mice to exercise by shaking stimuli to investigate the mechanisms of suppressing colorectal cancer, and focused on the Ca2+ pathway, which is one of the ß-catenin-independent Wnt signaling pathways that suppress the accumulation of ß-catenin. METHODS: Mice in the exercise group were subjected to exercise by shaking stimuli for 30 min/session, 6 sessions/ week, for a total of 11 weeks. The number and diameter of intestinal polyps were calculated. Expression analysis of ß-catenin and Pak1 from the intestinal tract and Wnt5a-Pan and Wnt5a-Long from the gastrocnemius muscle was performed by western blotting. The expression of ß-catenin and Wnt5a-Pan was observed by immunohistochemical staining. RESULT: The levels of expression of ß-catenin and Pak1 in the small intestine were low in the exercise group, indicating that exercise suppressed the accumulation of ß-catenin. In the gastrocnemius muscle, the levels of expression of Wnt5a-Pan and Wnt5a-Long were significantly higher in the exercise group (p < 0.05). Histological analysis revealed that the percentage of large polyps was significantly lower in the exercise group than in the control group (p < 0.01), revealing that exercise suppressed the growth of polyps. In addition, the villi/crypt ratio (V/C ratio) was significantly higher in the exercise group, suggesting the suppression of exercise-induced local inflammation in the small intestine. CONCLUSION: We believe that the mechanism of polyp growth suppression is related to the inflammatory and not the Wnt pathway. This study clarified the growth-suppressing effect of a novel exercise method on cancer. We believe that its development and clinical application might open new possibilities for the prevention treatment of colorectal cancer.

Novel shaking exercises for hippocampal and medial prefrontal cortex functioning maintain spatial working memory.

INTRODUCTION: The decline in spatial working memory is one of the earliest signs of normal brain aging. OBJECTIVE: We developed a novel physical exercise method, termed the "shaking exercise," to slow down this process. METHODS: The experimental protocol included administering the shaking exercise for 8-32 weeks in male senescence-accelerated mouse prone 10 (SAMP-10). They were subjected to the T-maze test, followed by immunohistochemical analysis, to assess the influence of the shaking exercise on the M1 muscarinic acetylcholine receptor (CHRM1) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) of the dorsal hippocampus and medial prefrontal cortex (dHC-mPFC). RESULTS: The T-maze test demonstrated that the shaking group had less hesitation in the face of selecting direction at week 24. In the immunohistochemical analysis, more CHRM1s were in the CA3 subregion and more AMPARs were in the subiculum. CHRM1s and AMPARs were maintained in the CA1 region and the mPFC. The CHRM1s seem to have a positive effect on the AMPAR in the dentate gyrus (DG) region and the CA3 region. In the CA1 region, CHRM1s were negatively correlated with AMPARs. In addition, high-density neurons were expressed in the shaking group in the upstream DG, the middle part and the distal part of CA3, the distal part of CA1, and the mPFC. CONCLUSIONS: Our results raise the possibility that maintenance of the spatial working memory effect observed with the shaking exercise is driven in part by the uneven affection of CHRM1s and AMPARs in the dHC-mPFC circuit system and significantly maintains the neuronal expression in the dHC-mPFC.

Exercise by Shaking Alleviates the Decline in Memory due to Aging: A Study in Mice.

INTRODUCTION: Although exercise can prevent cognitive decline due to aging, few elderly individuals are able to exercise for long. Therefore, an exercise method for older adults that is feasible for a long duration without overexertion is necessary. In this study, we focused on exercise by shaking. This study examined the possibility to prevent the decline in memory through regular and long-term shaking exercise using a senescence-accelerated mouse (SAM) model. Behavioral analysis was conducted, and histological changes in the mouse brain were examined to evaluate whether this stimulation method could become a novel exercise method. MATERIALS AND METHODS: The shaking exercise was applied to SAMP10 mice for 30 min 3 times per week for 25 continuous weeks. Behavioral analysis included a step-through passive avoidance test, whereas the histological analysis involved immunohistochemical staining using the anti-glutamate receptor (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors [AMPAR]) antibody in the hippocampus. The number and area of nerve cells in the hippocampal regions were measured and compared between groups. RESULTS: Behavioral analysis revealed that the shaking group retained memory longer than the control group, and memory capacity decline was suppressed. Additionally, histological examination showed that the shaking group had a higher number of AMPAR receptor-positive neurons per area in the hippocampal CA1 and CA3 regions than the control group, suggesting that degeneration and shedding of neurons due to aging was suppressed. DISCUSSION/CONCLUSION: We believe that shaking could become an exercise therapy that can reduce the decline in memory with aging and expect its human application in the future.

Use-dependent increase in attention to the prosthetic foot in patients with lower limb amputation.

Patients with lower limb amputation experience "embodiment" while using a prosthesis, perceiving it as part of their body. Humans control their biological body parts and receive appropriate information by directing attention toward them, which is called body-specific attention. This study investigated whether patients with lower limb amputation similarly direct attention to prosthetic limbs. The participants were 11 patients with lower limb amputation who started training to walk with a prosthesis. Attention to the prosthetic foot was measured longitudinally by a visual detection task. In the initial stage of walking rehabilitation, the index of attention to the prosthetic foot was lower than that to the healthy foot. In the final stage, however, there was no significant difference between the two indexes of attention. Correlation analysis revealed that the longer the duration of prosthetic foot use, the greater the attention directed toward it. These findings indicate that using a prosthesis focuses attention akin to that of an individual's biological limb. Moreover, they expressed that the prosthesis felt like a part of their body when they could walk independently. These findings suggest that the use of prostheses causes integration of visual information and movement about the prosthesis, resulting in its subjective embodiment.

Maintenance of the Amygdala-Hippocampal Circuit Function with Safe and Feasible Shaking Exercise Therapy in SAMP-10 Mice.

INTRODUCTION: Patients with dementia show reduced adaptive, behavioral, and physiological responses to environmental threats. Physical exercise is expected to delay brain aging, maintain cognitive function and, consequently, help dementia patients face threats and protect themselves skillfully. METHODS: To confirm this, we aimed to investigate the effects of the shaking exercise on the avoidance function in the senescence-accelerated mouse-prone strain-10 (SAMP-10) model at the behavioral and tissue levels. SAMP-10 mice were randomized into 2 groups: a control group and a shaking group. The avoidance response (latency) of the mice was evaluated using a passive avoidance task. The degree of amygdala and hippocampal aging was evaluated based on the brain morphology. Subsequently, the association between avoidance response and the degree of amygdala-hippocampal aging was evaluated. RESULTS: Regarding the passive avoidance task, the shaking group showed a longer latency period than the control group (p < 0.05), even and low intensity staining of ubiquitinated protein, and had a higher number of and larger neurons than those of the control group. The difference between the groups was more significant in the BA region of the amygdala and the CA1 region of the hippocampus (staining degree: p < 0.05, neuron size: p < 0.01, neuron counts: p < 0.01) than in other regions. CONCLUSIONS: The shaking exercise prevents nonfunctional protein (NFP) accumulation, neuron atrophy, and neuron loss; delays the aging of the amygdala and hippocampus; and maintains the function of the amygdala-hippocampal circuit. It thus enhances emotional processing and cognition functions, the memory of threats, the skillful confrontation of threats, and proper self-protection from danger.

Body-Specific Attention to the Hands and Feet in Healthy Adults.

To execute the intended movement, the brain directs attention, called body-specific attention, to the body to obtain information useful for movement. Body-specific attention to the hands has been examined but not to the feet. We aimed to confirm the existence of body-specific attention to the hands and feet, and examine its relation to motor and sensory functions from a behavioral perspective. The study included two groups of 27 right-handed and right-footed healthy adults, respectively. Visual detection tasks were used to measure body-specific attention. We measured reaction times to visual stimuli on or off the self-body and calculated the index of body-specific attention score to subtract the reaction time on self-body from that off one. Participants were classified into low and high attention groups based on each left and right body-specific attention index. For motor functions, Experiment 1 comprised handgrip strength and ball-rotation tasks for the hands, and Experiment 2 comprised toe grip strength involved in postural control for the feet. For sensory functions, the tactile thresholds of the hands and feet were measured. The results showed that, in both hands, the reaction time to visual stimuli on the hand was significantly lesser than that offhand. In the foot, this facilitation effect was observed in the right foot but not the left, which showed the correlation between body-specific attention and the normalized toe gripping force, suggesting that body-specific attention affected postural control. In the hand, the number of rotations of the ball was higher in the high than in the low attention group, regardless of the elaboration exercise difficulty or the left or right hand. However, this relation was not observed in the handgripping task. Thus, body-specific attention to the hand is an important component of elaborate movements. The tactile threshold was higher in the high than in the low attention group, regardless of the side in hand and foot. The results suggested that more body-specific attention is directed to the limbs with lower tactile abilities, supporting the sensory information reaching the brain. Therefore, we suggested that body-specific attention regulates the sensory information to help motor control.

Relationship Between Body-Specific Attention to a Paretic Limb and Real-World Arm Use in Stroke Patients: A Longitudinal Study.

Learned nonuse is a major problem in upper limb (UL) rehabilitation after stroke. Among the various factors that contribute to learned nonuse, recent studies have focused on body representation of the paretic limb in the brain. We previously developed a method to measure body-specific attention, as a marker of body representation of the paretic limb and revealed a decline in body-specific attention to the paretic limb in chronic stroke patients by a cross-sectional study. However, longitudinal changes in body-specific attention and paretic arm use in daily life (real-world arm use) from the onset to the chronic phase, and their relationship, remain unknown. Here, in a longitudinal, prospective, observational study, we sought to elucidate the longitudinal changes in body-specific attention to the paretic limb and real-world arm use, and their relationship, by using accelerometers and psychophysical methods, respectively, in 25 patients with subacute stroke. Measurements were taken at baseline (TBL), 2 weeks (T2w), 1 month (T1M), 2 months (T2M), and 6 months (T6M) after enrollment. UL function was measured using the Fugl-Meyer Assessment (FMA) and Action Research Arm Test (ARAT). Real-world arm use was measured using accelerometers on both wrists. Body-specific attention was measured using a visual detection task. The UL function and real-world arm use improved up to T6M. Longitudinal changes in body-specific attention were most remarkable at T1M. Changes in body-specific attention up to T1M correlated positively with changes in real-world arm use up to T6M, and from T1M to T6M, and the latter more strongly correlated with changes in real-world arm use. Changes in real-world arm use up to T2M correlated positively with changes in FMA up to T2M and T6M. No correlation was found between body-specific attention and FMA scores. Thus, these results suggest that improved body-specific attention to the paretic limb during the early phase contributes to increasing long-term real-world arm use and that increased real-world use is associated with the recovery of UL function. Our results may contribute to the development of rehabilitation strategies to enhance adaptive changes in body representation in the brain and increase real-world arm use after stroke.

Maintaining Aging Hippocampal Function with Safe and Feasible Shaking Exercise in SAMP10 Mice.

INTRODUCTION: The disabling effects of dementia, an incurable disease with little effect on mortality, affect society far more than many other conditions. OBJECTIVE: The aim of this study was to stop or delay the onset of dementia using low-cost methods such as physical exercise. METHODS: Senescence-accelerated model-prone (SAMP) 10 mice were made to perform a user-friendly shaking exercise for 25 weeks. The motor function and hippocampal functions (learning, spatial cognition) of the mice were evaluated using behavioral experiments. The degree of hippocampal aging was evaluated based on brain morphology. The association between behavioral performance of the mice and the degree of hippocampal aging was then evaluated. RESULTS: The behavioral test results showed that the shaking group had higher motor coordination (p < 0.01) and motor learning (p < 0.05). Significantly higher performances in the learning ability were observed in the shaking group at a middle-period experiment (p < 0.05); the spatial cognitive functions also improved (p < 0.05). The shaking group showed delayed ageing of cells in the dentate gyrus (DG; area: p < 0.01) and cornu Ammonis (CA; area: p < 0.01) regions of the hippocampus. CONCLUSIONS: The shaking exercise enhances the activity of mice and reduces age-associated decreases in learning and spatial cognitive functions. Regarding hippocampal morphology, shaking exercise can prevent non-functional protein accumulation, cell atrophy, and cell loss. Specifically, shaking exercise protects cell growth and regeneration in the DG area and enhances the learning function of the hippocampus. Furthermore, shaking exercise maintained the spatial cognitive function of cells in the CA3 and CA1 regions, and prevented the chronic loss of CA2 transmission that decreased the spatial memory decline in mice.

Time-dependent decline of body-specific attention to the paretic limb in chronic stroke patients.

OBJECTIVE: To examine whether reduced body-specific attention to a paretic limb is found in chronic stroke patients in a time-dependent manner. METHODS: Twenty-one patients with chronic hemiparesis (10 left and 11 right hemiparesis) after subcortical stroke and 18 age-matched healthy controls were recruited in this study. Standard neuropsychological examinations showed no clear evidence of spatial neglect in any patient. In order to quantitatively measure spatial attention to the paretic hand, a visual detection task for detecting a target appearing on the surface of either a paretic or dummy hand was used. This task can measure the body facilitation effect, which makes faster detection of a target on the body compared with one far from the body. RESULTS: In stroke patients, there was no difference in the reaction time for a visual target between the paretic and the dummy hands, while the healthy participants showed faster detection for the visual target on the real hand than on the dummy one. The index of the body facilitation effect, subtracting the reaction time for the target-on-paretic hand from that for the target-on-dummy one, was correlated with the duration since onset and with finger function test on the Stroke Impairment Assessment Set. CONCLUSIONS: The reduction of the body facilitation effect in the paretic limb suggests the decline of body-specific attention to the paretic one in patients with chronic hemiparesis. This decline of body-specific attention, leading to neglect for the paretic limb, will be one of the most serious problems for rehabilitation based on use-dependent plasticity.