Aerobic Treadmill Exercise Upregulates Epidermal Growth Factor Levels and Improves Learning and Memory in d-galactose-Induced Aging in a Mouse Model.

Previous studies have demonstrated that exercise improves cognitive function in Alzheimer's disease mice but the exact mechanism needs further studies. This research aimed to study the effects of aerobic treadmill exercise on epidermal growth factor (EGF) levels and learning and memory in d-galactose-induced aging in a mouse model. Forty male Kunming mice were analyzed in this study and randomly divided into 4 groups: control (C group), aerobic exercise (AE group), d-galactose (D-gal group), and d-galactose + aerobic exercise (D-gal + AE group). The C and AE groups received a daily mid-scapular subcutaneous injection of .9% saline for 40 days. Mice in the D-gal and D-gal + AE groups were subcutaneously injected with d-galactose (1.25 mg/kg) once daily for 40 days. The mice in the AE group and D-gal + AE group completed 40 days of aerobic treadmill exercise. Learning and memory were evaluated by step-down tests. Specifically, 24 h after the behavioral test, blood was collected and brain tissue was extracted, and superoxide dismutase (SOD) and acetylcholinesterase activities were detected. The neurons in the CA1 and CA3 regions of the hippocampus were counted by Nissl staining. The number of EGF-positive cells was observed by immunohistochemical methods. In the learning test, the reaction time in the D-gal group increased significantly (P < .05), while the error numbers in the D-gal group tended to decrease compared with AE, D-gal + AE, and C groups. In the memory test, the latency of mice in the D-gal group was lower, while the error in this group was higher than in the other groups (P < .05). The activities of SOD and acetylcholinesterase were lower in the D-gal group than in the other groups (P < .05). The number of EGF-positive cells and neurons in the hippocampal CA1 and CA3 regions in the D-gal + AE group was higher compared to those in the D-gal group (P < .05), and lower in groups with mice that were not injected with d-galactose. Aerobic treadmill exercise inhibited SOD activity, increased EGF-positive cells, and decreased neuronal death and apoptosis, thereby improving learning and memory in the mouse model of d-galactose-induced aging.

Aerobic Exercise Regulates Apoptosis through the PI3K/Akt/GSK-3ß Signaling Pathway to Improve Cognitive Impairment in Alzheimer's Disease Mice.

Neuronal apoptosis is an important factor in the etiology of Alzheimer's disease (AD). Aerobic exercise (AE) enhances learning and memory, improves cognitive impairment, increases telomere binding protein expression, and decreases apoptosis regulators, but it remains unclear whether it can improve cognitive impairment caused by neuronal apoptosis in AD. Therefore, this study investigated whether an 8-week running table exercise intervention could reduce apoptosis and improve cognitive function in the hippocampal neurons of AD model mice. After the exercise intervention, we evaluated the learning memory ability (positioning, navigation, and spatial search) of mice using a Morris water labyrinth, Nissl staining, immunohistochemistry, and protein application to detect hippocampal PI3K/Akt/GSK-3ß signaling pathway protein and hippocampal neuronal cell apoptosis protein B cell lymphoma 2 (Bcl-2) and apoptosis-promoting protein bcl-2-related X (Bax) protein expression. The results showed that aerobic exercise improved the location and spatial exploration ability of mice, increased the number of PI3K- and p-Akt-positive cells, increased the expression of PI3K, p-Akt, and bcl-2 proteins, decreased the expression of GSK-3ß and Bax proteins, and increased the bcl-2/Bax ratio of mice. The results suggest that aerobic exercise can reduce apoptosis and improve cognitive function in AD mice. The molecular mechanism may involve activation of the PI3K/Akt/GSK-3ß signaling pathway.

Medical expenditure for strabismus: a hospital-based retrospective survey.

BACKGROUND AND AIMS: The misconception of the purpose of strabismus treatment has, on the one hand, affected the motivation of strabismus patients to seek care and, on the other hand, has resulted in strabismus not being covered by health insurance, both of which interact to limit the motivation of strabismus patients and also impose a financial burden on strabismus patients. Previous studies on the cost of strabismus had only addressed the cost utility and functional and psychosocial benefits of strabismus surgery. The aim of this study was to estimate the direct medical expenditure incurred for strabismus surgery and analyze the trend for the period 2014-2019 using the data collected by local eye hospitals in northeast China. METHODS: This study was based on 6-year strabismus medical expenditure data collected from the eye hospital of the first affiliated hospital of Harbin medical university, covering 3596 strabismus patients who had strabismus surgery. All medical expenditure data were adjusted to 2014 using China's annual consumer price index to remove the effects of inflation. RESULTS: The average direct medical expenditure for strabismus cares (in 2014) was 5309.6 CNY (US$870.4), and the annual growth rates from 2015 to 2019 (compared with the previous year) were 9.3, 7.7, 21.7, 14.5, and 4.3%, respectively. Surgical expenses accounted for the highest proportion (33.1%) of the total medical expenses followed by examinations expenses (19.7%) and medical consumables expenses (18.7%). The regression coefficient for general anaesthesia was 1804.5 and age was less than 0. CONCLUSION: The average direct medical expenditure for strabismus increases year by year, and the growth rate is rapid. Anesthesia was the most important factor increasing medical cost, and age was negatively correlated with cost.

Brain source imaging based on movement-related cortical potentials induced by fatigue during self-paced handgrip contractions.

PURPOSE: By using standard low resolution electromagnetic tomography (sLORETA), we sought to explore the changes in brain source localization when performing right handgrip contractions in the condition of muscular fatigue. METHODS: Ten healthy adults volunteered for this study, and were asked to perform repeated and intermittent self-paced right handgrip contractions at 30% maximal voluntary contraction based on visual feedback leading to fatigue of right flexor digitorum profundus. Motor potentials from the movement-related cortical potentials were extracted from the electroencephalogram and were further analyzed by sLORETA. RESULTS: The activated cortical regions were mainly the Brodmann area 6 on the superior frontal and medial frontal gyri, and the BA 10 on the frontal and medial frontal gyri. With the development of muscular fatigue, current density of the motor potential significantly increased and the activated cortical areas markedly enlarged. CONCLUSION: In an attempt to maintain a target level of force during upper limb muscle fatigue induced by low intensity repetitive activation, the brain enhances the activation of sensorimotor cortex and enlarges the sensorimotor cortex area, especially in the ipsilateral hemisphere.

Perceived exertion during muscle fatigue as reflected in movement-related cortical potentials: an event-related potential study.

The aim of this study was to explore the mechanism on perceived exertion during muscle fatigue. A total of 15 individuals in the fatigue group and 13 individuals in the nonfatigue group were recruited into this study, performing 200 intermittent handgrip contractions with 30% maximal voluntary contraction. The force, surface electromyography (sEMG), movement-related cortical potentials (MRCPs), and rating perception of effort (RPE) were combined to evaluate the perceived exertion during muscle fatigue. The maximal handgrip force significantly decreased (P<0.01), the root mean square of sEMG over each block significantly increased (P<0.01), and SD of force at plateau increased (P<0.01) during muscle fatigue. The RPE scores reported by the individuals and the motor potential amplitude of MRCPs in the fatigue group significantly increased (P<0.001). However, as for the individuals in the nonfatigue group, the other indexes showed no significant changes except for a little increase in the RPE. The within-subject correlation coefficients showed that there were significant correlations between RPE and motor potential amplitude of MRCPs at the C1 site (r=-0.609, P<0.001) and between RPE and root mean square of sEMG (r=0.541, P<0.001). Our results substantiate that the perceived exertion correlates with the central motor command during movement execution rather than the preparatory process. The perceived exertion not only reflects central fatigue but could also reflect the peripheral local muscle fatigue.

Movement-related cortical potentials during muscle fatigue induced by upper limb submaximal isometric contractions.

The aim of this study was to examine the central neurophysiological mechanisms during fatigue induced by submaximal isometric contractions. A total of 23 individuals participated in the study and were assigned to fatigue and nonfatigue groups. Handgrip force, root mean square (RMS) of surface electromyography (sEMG) signal and movement-related cortical potentials during self-paced submaximal handgrip isometric contractions were assessed for each participant. The experimental data showed significant decreases in both maximal voluntary contraction [-24.3%; F(3, 42)=19.62, P<0.001, ηp=0.48] and RMS [-30.1%; F(3, 42)=19.01, P<0.001, ηp=0.57] during maximal voluntary contractions and a significant increase [F(3, 42)=14.27, P<0.001, ηp=0.50] in the average RMS of sEMG over four blocks in the fatigue group. There was no significant difference in the readiness potential between the fatigue and the nonfatigue groups at early stages, and at late stages, significant differences were observed only at the Fp1 and FC1 sites. Motor potential amplitudes were significantly higher in the fatigue group than in the nonfatigue group irrespective of block or electrode positions. Positive waveforms were observed in the prefrontal cortex in states without muscle fatigue, whereas a negative waveform pattern was observed with muscle fatigue. Significant within-subject correlations were observed between motor potential at the C1 site and RMS of sEMG (r=-0.439, P=0.02, ηp=0.11). Neurophysiological evidence indicates that cortical activity increases in the prefrontal cortex, primary motor cortex and supplementary motor cortex with muscle fatigue. Muscle fatigue appears to have considerable effects on the components of movement-related cortical potentials during movement execution, whereas the readiness potential before movement is sensitive to cognitive demands during prolonged exercise. Our results provide additional evidence for a link between central motor command during movement execution and motor unit recruitment.

Effect of p62 on tau hyperphosphorylation in a rat model of Alzheimer's disease.

Tau hyperphosphorylation is a main cause of neuronal loss in Alzheimer's disease, which can be caused by many factors, including oxidative stress. The multifunctional protein p62, which exists in neurofibrillary tangles and causes aggregation of hyperphosphorylated tau, not only serves as a receptor in selective autophagy, but also regulates oxidative stress. However, whether p62 participates in oxidative stress-induced tau hyperphosphorylation remains unclear. In this study, we produced an Alzheimer's disease rat model by injecting ß-amyloid protein into the hippocampus and ß-galactose intraperitoneally. Hematoxylin-eosin staining was used for morphological analysis of brain tissue, and western blotting, immunohistochemistry and reverse transcription-PCR were employed to study p62 and autophagy related proteins, antioxidant defense system kelch-like ECH-associated protein 1-NF-E2-related factor 2 related proteins and hyperphosphorylated tau, respectively. The number of neurons in the brain decreased in Alzheimer's disease rats, and the autophagy related proteins Atg12-Atg5, microtubule-associated protein 1 light chain 3-phosphatidylethanolamine and Beclin1 increased significantly, while p62 expression reduced. Expression of kelch-like ECH-associated protein 1 increased, NF-E2-related factor 2 protein and the downstream gene products of glutamate cysteine ligase catalytic subunit and glutamate cysteine ligase modulatory subunit decreased, and hyperphosphorylated tau increased. These findings demonstrate that autophagy levels increased and p62 levels decreased in the brains of Alzheimer's disease rats. Moreover, the anti-oxidative capability of the NF-E2-related factor 2-antioxidant response element pathway was decreased, which may be the cause of tau hyperphosphorylation in Alzheimer's disease brain tissue and the subsequent structural and functional damage to neurons.

[Women boxing athletes' EMG of upper limbs and lumbar muscles in the training of air striking of straight punch].

OBJECTIVE: To study training effect of upper limbs and lumbar muscles in the proceed of air striking of straight punch by analyzing boxing athletes' changes of electromyogram (EMG). METHODS: We measured EMG of ten women boxing athletes' upper arm biceps (contractor muscle), upper arm triceps (antagonistic muscle), forearm flexor muscle (contractor muscle), forearm extensor muscle (antagonistic muscle), and lumbar muscles by ME6000 (Mega Electronics Ltd.). The stipulated exercise was to do air striking of straight punch with loads of 2.5 kg of dumbbell in the hand until exhausted. RESULTS: In the proceed of exercise-induce exhausted, the descend magnitude and speed of median frequency (MF) in upper limb antagonistic muscle exceeded to contracting muscle, moreover, the work percentage showed that contractor have done a larger percentage of work than antagonistic muscle. Compared with world champion's EMG, the majority of ordinary athletes' lumbar muscles MF revealed non-drop tendency, and the work percentage showed that lumbar muscles had a very little percentage of work. CONCLUSION: After comparing the EMG test index in upper limb and lumbar muscle of average boxing athletes with that of the world champion, we find the testees lack of the training of upper limb antagonistic muscle and lumbar muscle, and more trainings aimed at these muscles need to be taken.

Intracerebroventricular injection of trazodone produces 5-HT receptor subtype mediated anti-nociception at the supraspinal and spinal levels.

Serotonin (5-HT) mediated anti-nociceptive effects induced by an anti-depressant, trazodone, are related to 5-HT(1A) receptor activities at the supraspinal level. 5-HT(3) receptor activation via the descending anti-nociceptive pathways may contribute to the trazodone mediated anti-nociception at the spinal level. Intracerebroventricular (i.c.v.) injection of trazodone dose-dependently impaired nociceptive responses in the formalin test in mice. Six and 15 microg of trazodone inhibited the early (P<0.05 or 0.01) and the late phases of the formalin test (P<0.05 or 0.01), while 3 microg had no effect. We examined the effects of a selective 5-HT(1A) receptor antagonist, WAY-100635, a single injection of which induced hyperalgesia (P<0.05), and blocked the anti-nociceptive effects of trazodone (P<0.01) when the two were simultaneously injected i.c.v. Intrathecal (i.t.) injection of a selective 5-HT(3) receptor antagonist, 3-tropanylindole-3-carboxylate hydrochloride, blocked the anti-nociceptive effects of i.c.v. trazodone (P<0.01), while WAY-100635 (i.t.) did not impair trazodone mediated anti-nociception. Trazodone mediated anti-nocicepton is related to serotonergic activity at both the supraspinal and the spinal level.

Mechanical stimulation activates small fiber mediated nociceptive responses in the nucleus gigantocellularis.

We characterized nociceptive discharges induced by mechanical stimulation and the modulating effects of orphanin FQ on noxious responses in the rat brain stem gigantocellular reticular nucleus (Gi). A pressure pulse of constant force and rising rate was delivered by a mechanical stimulator with feedback control, allowing responses to be analyzed statistically. A pressure pulse of 300 g, which evoked C-fiber mediated nerve responses, was delivered to the tail. Two excitatory (45/58) and one inhibitory (13/58) types of extracellular unit discharges were recorded in Gi. One of the excitatory types was a phasic discharge (13/45) elicited at the onset and/or the end of stimulation. Latencies of the phasic discharges (0.104+/-0.1 s) were shorter than those of other type (tonic) discharges (0.43+/-0.2 s). The tonic discharges (32/45), which frequently persisted past the end of stimulation without adaptation, were classified into two groups. The first group of tonic type units (23/45) was high threshold, like nociceptive specific neurons in the primary sensory cortex, while the second group of neurons (9/45) responded to a wide range of stimulus intensities. The mean frequency, response duration and spike numbers gradually increased with stimulus intensity change in all nine neurons. The neurons encode mechanical stimulus intensity with discharge frequency, response duration and evoked spike numbers. Local injection of orphanin FQ (200 ng/2 microl) changed high threshold tonic type spike numbers in a biphasic manner, i.e., there was an early phase suppression (5-30 min, p=0.016) and a late phase enhancement (30-60 min, p=0.027). In contrast, phasic type discharges did not show an altered discharge pattern in response to orphanin FQ. Thus, orphanin FQ affects small fiber-mediated nociceptive responses and may behave as a complex modulator of pain systems in the brain stem.