Excessive Aβ deposition in the brain is associated with the formation of senile plaques, and their diffuse distribution is related to Alzheimer's disease. Thirty rats (EG) were irradiated with light-emitting diode (photobiomodulation (PBM)) in the frontal region of the skull after being inoculated with the Aβtoxin in the hippocampus; 30 rats were used as the control group (CG). The analysis was conducted at 7, 14, and 21 days after irradiation. We observed a decreased in Aβ deposits in treated animals compared with animals in the CG. The behavioral and motor assessment revealed that the EG group covered a larger ground distance and explored the open field than the CG group on days 14 and 21 (p < 0.05). The EG group was statistically significant in the spatial memory test compared to the CG group on day 14. The use of PBM significantly reduced the presence of Aβ plaques and improved spatial memory and behavioral and motor skills in treated animals on day 21.

Diabetes mellitus is considered as a risk factor for Alzheimer disease. The aim of the present study was to evaluate the possibility whether treadmill exercise ameliorates Alzheimer disease-associated memory loss in the diabetes mellitus. For this study, the effects of treadmill exercise on short-term memory and spatial learning ability in relation with Wnt signaling pathway were evaluated using the streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by intraperitoneal injection of STZ. Step-down avoidance task and 8-arm radial maze test were performed for the memory function. Immunohistochemistry for 5-bro-mo-2'-deoxyridine (BrdU) and doublecortin (DCX) and Western blot for Wnt3 and glycogen synthase kinase-3β (GSK-3β) were conducted. The rats in the exercise groups were made to run on the treadmill for 30 min per one day, 5 times a week, during 12 weeks. In the present results, short-term memory and spatial learning ability were deteriorated by induction of diabetes. Treadmill exercise improved short-term memory and spatial learning ability in the diabetic rats. The numbers of BrdU-positive and DCX-positive cells in the hippocampal dentate gyrus were decreased by induction of diabetes. Treadmill exercise increased these numbers in the diabetic rats. Wnt3 expression in the hippocampus was decreased and GSK-3β expression in the hippocampus was increased by induction of diabetes. Treadmill exercise increased Wnt3 expression and suppressed GSK-3β expression in the diabetic rats. The present study suggests that treadmill exercise alleviates Alzheimer disease-associated memory loss by increasing neurogenesis through activating Wnt signaling pathway in the diabetic rats.

Autism is a complex developmental disorder with impairments in social interaction, communication, repetitive behavior and motor skills. Exercise enhances cognitive function, ameliorates motor dysfunction, and provides protective profits against neurodegeneration. In the present study, we evaluated the effect of treadmill exercise on the motor coordination and Purkinje cell loss in relation with reactive astrocytes and microglial activation in the cerebellum using valproic acid (VPA)-induced autism rat model. On the 12th day of pregnancy, the pregnant rats in the VPA-exposed group received intraperitoneal injections of 600-mg/kg VPA. After birth, the rat pups were divided into four groups: the control group, the exercise group, the VPA-treated group, the VPA-treated and exercise group. The rat pups in the exercise groups were forced to run on a treadmill for 30 min once a day, 5 times a week for 4 weeks. In the present results, motor balance and coordination was disturbed by induction of autism, in contrast, treadmill exercise alleviated motor dysfunction in the autistic rats. Purkinje cell loss, reactive astrocytes, and microglial activation were occurred by induction of autism, in contrast, treadmill exercise enhanced survival rate of Purkinje neurons through inhibition of reactive astrocytes and microglia in the autistic rats. The present study showed that exercise may provide a potential therapeutic strategy for the alleviation of motor dysfunction in autistic patients.

Alzheimer disease (AD) is a most common form of dementia and eventually causes impairments of learning ability and memory function. In the present study, we investigated the effects of treadmill exercise on the symptoms of AD focusing on the microglial activation-induced apoptosis. AD was made by bilateral intracerebroventricular injection of streptozotocin. The rats in the exercise groups were made to run on a treadmill once a day for 30 min during 4 weeks. The distance and latency in the Morris water maze task and the latency in the step-down avoidance task were increased in the AD rats, in contrast, treadmill exercise shortened these parameters. The numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive and caspase-3-positive cells in the hippocampal dentate gyrus were decreased in the AD rats, in contrast, treadmill exercise suppressed these numbers. Expressions of glial fibrillary acidic protein (GFAP) and cluster of differentiation molecule 11B (CD11b) in the hippocampal dentate gyrus were increased in the AD rats, in contrast, treadmill exercise suppressed GFAP and CD11b expressions. Bax expression was increased and Bcl-2 expression was decreased in the hippocampus of AD rats, in contrast, treadmill exercise decreased Bax expression and increased Bcl-2 expression. The present results demonstrated that treadmill exercise ameliorated AD-induced impairments of spatial learning ability and short-term memory through suppressing apoptosis. The antiapoptotic effect of treadmill exercise might be ascribed to the inhibitory effect of treadmill exercise on microglial activation.

AIMS:Treadmill exercise is a beneficial treatment following childhood stroke. Thus, studies focusing on the neuroprotective mechanism of exercise training during postischemic treatment in children with ischemic stroke are urgently needed. We evaluated the effects of treadmill exercise on autophagy after cerebral ischemia in young rats.

MAIN METHODS:Rats (23-25 days old) underwent cerebral ischemia-reperfusion (CI/R) surgery. The experimental animals were divided into 5 groups, and some groups received either treadmill exercise, a rapamycin (RAPA) injection or combination therapy for 3 or 7 days. We performed a series of experimental tests including neurological scoring, hematoxylin-eosin staining (H&E), Nissl staining, triphenyl tetrazolium chloride (TTC) staining, Western blot analysis (WB), immunofluorescence (IF), enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy (TEM) and Terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) fluorescence.

KEY FINDINGS:The experimental data indicated that treadmill exercise inhibited autophagy in the ischemic penumbra, inhibited high mobility group box 1 (HMGB1) translocation and binding to Beclin1, reduced apoptosis, reduced infarct volumes, and aided in functional recovery. However, RAPA promoted the opposite effects of treadmill exercise.

SIGNIFICANCE:We found that treadmill exercise improves the neurological deficits induced by CI/R by inhibiting autophagy and HMGB1 binding to Beclin1.

BACKGROUND:Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by polyglutamine (CAG) expansion in the Huntingtin (HTT) gene. The CAGknock-in (KI) mouse model recapitulates the progression of motor symptoms emerging at 12 months of age.

OBJECTIVE:This study was aimed at assessing the effects of exercise, in the form of treadmill running, and examining its impact on motor behavior and markers of metabolism in the CAGKI mouse model of HD after motor symptoms have emerged.

METHODS:CAGKI mice at 13-15 months of age were subjected to treadmill exercise 3 days per week for 1 h per day or remained sedentary. After 12 weeks of exercise brain tissues were analyzed for enzymatic activity including mitochondria Complexes I, II/III, and IV, transglutaminase, aconitase, pyruvate dehydrogenase, and phosphofructokinase1/2. In addition, the concentration was determined for nitrate/nitrite, pyruvate carboxylase, NAD/NADH, and glutamate as well as the ratio of mitochondria and nuclear DNA. Motor behavior was tested using the rotarod.

RESULTS:Exercise resulted in increased [nitrite + nitrate] levels (surmised as nitric oxide), reduced transglutaminase activity, increased aconitase activity with increased tricarboxylic acid-generated reducing equivalents and mitochondrial oxidative phosphorylation complexes activity. Mitochondrial function was strengthened by increases in glycolysis, pyruvate dehydrogenase activity, and anaplerosis component represented by pyruvate carboxylase.

CONCLUSIONS:These changes in mitochondrial function were associated with improved motor performance on the rotarod test. These findings suggest that exercise may have beneficial effects on motor behavior by reversing deficits in mitochondrial function in a rodent model of HD.

Studies demonstrate that asthma, especially during childhood, affects the functions of the brain including learning and memory. Exercise is well known for its neuroprotective functions and for its beneficial effects on asthma. We aimed to assess the effects of exercise on cognitive function, synaptic plasticity, and hippocampal brain-derived neurotrophic factor (BDNF) levels in ovalbumin (OVA) sensitized juvenile rats. Rats were sensitized by intraperitoneal administration and inhaled OVA. Animals were subjected to treadmill running exercise during the OVA-challenged period. T-helper type 2 (Th2) cytokine [interleukin (IL)-4], Th1 cytokine (INF-γ) levels, and INF-γ/IL-4 (Th1/Th2) ratio in bronchoalveolar lavage fluid (BALF), and tracheal response to methacholine and OVA were measured. Further, memory behaviors and BDNF levels were measured in the hippocampus as well as long-term potentiation (LTP) was assessed by recording field excitatory postsynaptic potentials (fEPSPs) in the hippocampus. The levels of IL-4 and TGF-β were decreased but INF-γ level and INF-γ/IL-4 ratio increased in the BALF due to exercise in the OVA-sensitized animals. In addition, exercise improved OVA-sensitization induced cognitive impairments, increased BDNF levels, and enhanced hippocampal LTP in OVA-sensitized rats. Exercise is not only effective in the alleviation of airway inflammation by restoring Th1/Th2 cytokines balance, but also is a candidate for improvement of memory and synaptic plasticity deficits partially through increasing the levelsof hippocampal BDNF in OVA-sensitized rats.

BACKGROUND:Oxaliplatin is frequently used in the treatment of metastatic colorectal cancer. However, peripheral neuropathy is a severe adverse effect of oxaliplatin that may persist and impact quality of life.

OBJECTIVE:To assess the potential effects of ultrasound acupuncture for the alleviation of symptoms related to oxaliplatin-induced peripheral neuropathy (OIPN) among metastatic colorectal cancer patients.

DESIGN:A prospective cohort pilot study.

SETTING:Education and research hospital.

PARTICIPANTS:Patients with a diagnosis of stages II-IV colorectal cancer treated with oxaliplatin-based treatment regimens and with the presence of OIPN symptoms (n = 17).

INTERVENTIONS:Pulsed therapeutic ultrasound (1 MHz) at bilateral acupuncture points of PC6, PC7, BL60 and KI1 were administered for 5 min/point daily for 12 d.

MAIN OUTCOME MEASURES:Pain Quality Assessment Scale (PQAS), Chemotherapy-induced Neurotoxicity Questionnaire (CINQ), quantitative touch-detection threshold, cold-trigger pain withdrawal latency and quality of life (EORTC QLQ-C30) were measured at baseline (day 0), pre-intervention (day 12, post wash-out period), post-intervention (day 24) and final follow-up (day 54). A P values of less than 0.05 was considered statistically significant.

RESULTS:Scores of PQAS and CINQ significantly improved post ultrasound acupuncture at post-intervention and follow up compare to both base-line and pre-intervention. Similar trends were also observed for the Quantitative Sensory Testing where touch-detection threshold significantly decreased and cold-trigger pain withdrawal latency significantly increased post ultrasound acupuncture. Patients also showed an improvement on Quality of Life outcomes as measured by QLQ-C30 post-intervention and at follow up.

CONCLUSIONS:Ultrasound acupuncture could potentially be an effective intervention for OIPN symptoms for colorectal cancer patients. However, larger and randomized clinical trials with placebo controls are needed to confirm such effect. This article is protected by copyright. All rights reserved.

BACKGROUND:When performing two tasks at once, a dual task, performance on one or both tasks typically suffers. People with Parkinson's disease (PD) usually experience larger dual task decrements on motor tasks than healthy older adults (HOA). Our objective was to investigate the decrements in cycling caused by performing cognitive tasks with a range of difficulty in people with PD and HOAs.

METHODS:Twenty-eight participants with Parkinson's disease and 20 healthy older adults completed a baseline cycling task with no secondary tasks and then completed dual task cycling while performing 12 tasks from six cognitive domains representing a wide range of difficulty.

RESULTS:Cycling was faster during dual task conditions than at baseline, and was significantly faster for six tasks (all p<.02) across both groups. Cycling speed improved the most during the easiest cognitive tasks, and cognitive performance was largely unaffected. Cycling improvement was predicted by task difficulty (p<.001). People with Parkinson's disease cycled slower (p<.03) and showed reduced dual task benefits (p<.01) than healthy older adults.

CONCLUSIONS:Unexpectedly, participants' motor performance improved during cognitive dual tasks, which cannot be explained in current models of dual task performance. To account for these findings, we propose a model integrating dual task and acute exercise approaches which posits that cognitive arousal during dual tasks increases resources to facilitate motor and cognitive performance, which is subsequently modulated by motor and cognitive task difficulty. This model can explain both the improvement observed on dual tasks in the current study and more typical dual task findings in other studies.

Hypothyroidism causes an imbalance in antioxidant and pro-oxidants criteria in the brain and enhances the concentration of reactive oxygen species (ROS), and neuronal damage has been observed following an excessive ROS. The main purpose of this study was to examine the preventive effect of vitamin C on hypothyroidism associated neuronal damage in the hippocampus of neonatal and juvenile rats. Pregnant rats after delivery of their pups were randomly divided into four groups and treated with (1) normal drinking water as a control group, (2) Propylthiouracil (PTU) 0.005% added to drinking water, (3-4) PTU+VitC 10mg/kg and PTU+VitC 100mg/kg to drinking water. Treatment was carried out during rat's lactation period until to the postnatal day (PND) 60. To assess the histological and stereological changes that occur in this study, brains of 5 male pups were extracted. The number of dark neurons and apoptotic cells in the hippocampal sub-regions of PTU group was significantly greater than the control group's hippocampal sub-regions. In addition, hypothyroidism induced a reduction in the hippocampal volume and increased the numerical density and the total amount of dark neurons. The vitamin C only dose of 100mg/kg significantly reduced the number of dark neurons and apoptotic cells (P<0.01) and considerably weakened the influence of hypothyroidism on the volume reduction of the hippocampus (P<0.05). The current study suggested that vitamin C administration has a possibility to prevent hippocampal neuronal damage caused by neonatal and juvenile hypothyroidism in rats.

The present study evaluated the synergistic effects of the association of ascorbic acid andα-tocopherol on myenteric in the jejunum of diabetic rats. The rats were randomly divided into four equal groups: untreated normoglycemic (UC), untreated diabetic (UD), ascorbic acid and α-tocopherol-treated normoglycemic (CAE) and ascorbic acid and α-tocopherol-treated diabetic (DAE). The rats from the CAE and DAE group received supplementation with ascorbic acid (1g/L in water) and α-tocopherol (1% in chow). At 210-days-old, the animals were sacrified and their jejunum was collected and submitted to immunohistochemistry. Quantitative and/or morphometric analysis were performed. Supplementation with ascorbic acid and α-tocopherol prevented the cell loss of myenteric neurons expressing HuC/D and TrkA in an equivalent proportion. We also observed a reduction of the CGRP nerve fiber varicosities and the prevention of the increased cell body size of submucosal VIP neurons (p<0.05). The association of ascorbic acid andα-tocopherol reduced the deleterious effects of diabetes promoting protection on the enteric neurons.

Exercise has been shown to be protective against the risk of dementias, including Alzheimer's disease (AD). Intervention studies have demonstrated its ability to mitigate cognitive and behavioral impairments and reduce disease in both humans and animals. However, information is lacking in regard to the volume and intensity, as well as timing of exercise onset with respect to disease stage, which produces optimal benefits. Here, utilizing the Tg2576 mouse, a model of AD-like parenchymal amyloid pathology and cognitive impairment, we sought to understand the effects of different lengths of daily access to a running wheel on advanced stage disease. This study is the first to determine the benefits of long-term exercise (4 months of voluntary running) and different periods of daily access to a running wheel (0 h, 1 h, 3 h, and 12 h running wheel access) beginning in 14-month-old Tg2576 mice, an age with significant amyloid pathology. We found that exercising Tg2576 animals showed lower levels of some aspects of AD pathology and reduced behavioral dysfunction compared to sedentary Tg2576 animals.High intensity exercise, rather than high volume exercise, was generally most beneficial in reducing amyloid pathology. Our results suggest that engaging in vigorous exercise programs, even after living a sedentary life, may lead to a measurable reduction in AD pathology and preservation of some cognitive abilities.

Aim:This study was aimed at investigating the effects and molecular mechanisms of physical activity intervention on Parkinson's disease (PD) and providing theoretical guidance for the prevention and treatment of PD.

Methods:Four electronic databases up to December 2019 were searched (PubMed, Springer, Elsevier, and Wiley database), 176 articles were selected. Literature data were analyzed by the logic analysis method.

Results:(1) Risk factors of PD include dairy products, pesticides, traumatic brain injury, and obesity. Protective factors include alcohol, tobacco, coffee, black tea, and physical activity. (2) Physical activity can reduce the risk and improve symptoms of PD and the beneficial forms of physical activity, including running, dancing, traditional Chinese martial arts, yoga, and weight training. (3) Different forms of physical activity alleviate the symptoms of PD through different mechanisms, including reducing the accumulation of-syn protein, inflammation, and oxidative stress, while enhancing BDNF activity, nerve regeneration, and mitochondrial function.

Conclusion:Physical activity has a positive impact on the prevention and treatment of PD. Illustrating the molecular mechanism of physical activity-induced protective effect on PD is an urgent need for improving the efficacy of PD therapy regimens in the future.