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In brief Mealtime changes in pregnant mice revealed impaired neurobehavioral development in mouse offspring. This study is the basis for investigating diseases associated with neurobehavioral development of adult offspring of pregnant shift-working women. Abstract Most organisms on Earth have a biological clock, and their physiological processes are regulated by a 1-day cycle. In modern society, several factors can disturb these biological clocks in humans; in particular, individuals working in shifts are exposed to stark environmental changes that interfere with their biological clock. They have a high risk of various diseases. However, there are scarce experimental approaches to address the reproductive and health consequences of shift work in the offspring of exposed individuals. In this study, considering the fact that shift workers usually have their meals during their adjusted working time, we aimed to examine the effects of a 12-h shift with usual mealtime as a plausible night work model on the neurobehavioral development of adult mouse offspring. In these offspring, early exposure to this mealtime shift differentially affected circadian rhythmic variables and total locomotor activity depending on the timing and duration of restrictive feeding. Moreover, neurobehavioral alterations such as declined short-term memory and depressive-like behavior were observed in adulthood. These results have implications for the health concerns of shift-working women and their children.

Polydeoxyribonucleotide (PDRN), which is adenosine A2A receptor agonist, facilitates healing and inhibits inflammation and apoptosis. The effect of PDRN on alcoholic liver injury (ALI) was evaluated focusing on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. The mice were given daily oral administration of 50% ethanol at a dose of 4 g/kg during 8 weeks. After 4 weeks of alcohol intake, 200 μL of normal saline containing 8-mg/kg PDRN was intraperitoneally administered 3 times a week for 4 weeks. To determine whether the action of PDRN occurs through the adenosine A2A receptor, 8-mg/kg 3,7-dimethyl-1-propargylxanthine (DMPX) with PDRN was treated. The concentration of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was detected. For liver histopathological score, hematoxylin and eosin staining was conducted. Enzyme-linked immunoassay was used to measure cyclic adenosine-3′,5′-monophosphate (cAMP) concentration. PI3K and Akt expression was determined using Western blot analysis. In the results, PDRN treatment suppressed AST and ALT level in serum and liver tissue, and improved damaged liver tissue and decreased histological score. PDRN application inhibited the expression of phosphorylated PI3K/Akt signaling pathway. The increasing effect of PDRN on cAMP level ats as a mechanism for ALI treatment. Co-treatment of DMPX with PDRN did not reduce apoptosis, causing no improvement in liver function. As a result of this experiment, PDRN has the potential to be selected as a therapeutic agent for ALI.

Alzheimer's disease (AD) is a progressive degenerative brain disease and the primary cause of dementia. At an early stage, AD is generally characterized by short-term memory impairment, owing to dysfunctions of the cortex and hippocampus. We previously reported that a combination of exercise and 40-Hz light flickering can protect against AD-related neuroinflammation, gamma oscillations, reduction in Aβ, and cognitive decline. Therefore, we sought to extend our previous findings to the 5-mo-old 3×Tg-AD mouse model to examine whether the same favorable effects occur in earlier stages of cognitive dysfunction. We investigated the effects of 12 wk of exercise combined with 40-Hz light flickering on cognitive function by analyzing neuroinflammation, mitochondrial function, and neuroplasticity in the hippocampus in a 3×Tg-AD mouse model. Five-month-old 3×Tg-AD mice performed 12 wk of exercise with 40-Hz light flickering administered independently and in combination. Spatial learning and memory, long-term memory, hippocampal Aβ, tau, neuroinflammation, proinflammatory cytokine expression, mitochondrial function, and neuroplasticity were analyzed. Aβ and tau proteins levels were significantly reduced in the early stage of AD, resulting in protection against cognitive decline by reducing neuroinflammation and proinflammatory cytokines. Furthermore, mitochondrial function improved, apoptosis was reduced, and synapse-related protein expression increased. Overall, exercise with 40-Hz light flickering was significantly more effective than exercise or 40-Hz light flickering alone, and the improvement was comparable to the levels in the nontransgenic aged-match control group. Our results indicate a synergistic effect of exercise and 40-Hz light flickering on pathological improvements in the hippocampus during early AD-associated cognitive impairment.

This study attempted to investigate the association between changes in the intestinal environment and the brain using a model that received aerobic exercise and microbiome transplantation. All mice were fed a diet containing 60% fat. For the obesity with nonexercise microbiome transplantation group, feces from donors that did not undergo exercise were administered. For the obesity with exercise microbiome trans-plantation group, feces from donors who underwent exercise were ad-ministered. Treadmill exercise started 16 weeks after the intake of the high fat feeding and continued for 24 weeks. The short-term memory and spatial learning memory were determined by step-down avoidance test and Morris water maze task, immunohistochemistry for glial fibril-lary acidic protein, western blot analysis for brain-derived neurotrophic factor and tropomyosin receptor kinase B were performed in the hippo-campus. Exercise was the most effective way to reduce obesity, im-prove memory function, suppress inflammation, and increase brain-de-rived neurotrophic factor expression. Intestinal microbiota transplanta-tion was the second most effective after exercise. However, there was no significant difference in the fecal microbiota transplant group ac-cording to whether or not exercise was performed.

Neuronal cell death in the hippocampus by cerebral ischemia causes disability of memory function. Cerebral ischemia also alters the expressions of brain-derived neurotrophic factor (BDNF), cyclic adenosine monophosphate-responsive element binding protein (CREB), extracellular signal-regulated protein kinase (ERK), and phosphatidylinositol 3-kinase/protein kinase B (Akt). In the present study, we investigated the effect of treadmill exercise on cerebral ischemia in relation with ERK-Akt-CREB-BDNF signaling pathway in the hippocampus using gerbils. Induction of cerebral ischemia deteriorated short-term memory with suppression of phosphorylation of ERK-Akt-CREB-BDNF pathway in the hippocampus of gerbils. Enhancement of apoptosis in the hippocampus was accompanied in the ischemia gerbils. Treadmill exercise improved short-term memory through enhancing phosphorylation of ERK-Akt-CREB-BDNF pathway with suppressing apoptosis in the hip-pocampus of the ischemia gerbils. The present results suggest that improvement of memory function after cerebral ischemia by treadmill exercise may be involved in the ERK-Akt-CREB-BDNF signaling pathway, resulting in inhibition of apoptosis in the hippocampus.

Aging is associated with vulnerability to cardiovascular diseases, and mitochondrial dysfunction plays a critical role in cardiovascular disease pathogenesis. Exercise training is associated with benefits against chronic cardiac diseases. The purpose of this study was to determine the effects of aging and treadmill exercise training on mitochondrial function and apoptosis in the rat heart. Fischer 344 rats were divided into young sedentary (YS; n = 10, 4 months), young exercise (YE; n = 10, 4 months), old sedentary (OS; n = 10, 20 months), and old exercise (OE; n = 10, 20 months) groups. Exercise training groups ran on a treadmill at 15 m/min (young) or 10 m/min (old), 45 min/day, 5 days/week for 8 weeks. Morphological parameters, mitochondrial function, mitochondrial dynamics, mitophagy, and mitochondria-mediated apoptosis were analyzed in cardiac muscle. Mitochondrial O2 respiratory capacity and Ca2+ retention capacity gradually decreased, and mitochondrial H2O2 emitting potential significantly increased with aging. Exercise training attenuated aging-induced mitochondrial H2O2 emitting potential and mitochondrial O2 respiratory capacity, while protecting Ca2+ retention in the old groups. Aging triggered imbalanced mitochondrial dynamics and excess mitophagy, while exercise training ameliorated the aging-induced imbalance in mitochondrial dynamics and excess mitophagy. Aging induced increase in Bax and cleaved caspase-3 protein levels, while decreasing Bcl-2 levels. Exercise training protected against the elevation of apoptotic signaling markers by decreasing Bax and cleaved caspase-3 and increasing Bcl-2 protein levels, while decreasing the Bax/Bcl-2 ratio and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive myonuclei. These data demonstrate that regular exercise training prevents aging-induced impairment of mitochondrial function and mitochondria-mediated apoptosis in cardiac muscles.

Accurate measurement of static and dynamic forces during machining operations is important in the process monitoring, optimization and prediction of machining quality. Cutting and clamping forces are typically measured separately, for example, through hydraulic clamping force devices and piezoelectric table dynamometers. Since cutting and clamping forces interact throughout machining, both forces need to be measured simultaneously to accurately predict machining quality. This paper proposes a novel force measuring device in the form of a vise with built-in piezoelectric sensors and strain gauges to measure multi-axial clamping and cutting forces simultaneously. A strain concentrating design based on a cross-shaped groove was utilized to attach three strain gauges to measure clamping forces. These locations were chosen for their ability to measure clamping forces in real-time and minimize cross-talks. Piezoelectric sensors were embedded between layers in the vise jaw to measure cutting forces. A prototype of the proposed apparatus was fabricated and used to experimentally investigate sensitivities, bandwidth, clamping forces and cutting forces. The results showed that the proposed device has good performance in measuring clamping and cutting forces in milling operations.

The selective α2-adrenergic receptor agonist dexmedetomidine acts as an analgesic, sedative, and anesthetic adjuvant. The most common consequence of sleep deprivation is memory impairment. We investigated whether dexmedetomidine can counteract memory impairment caused by sleep deprivation and suppress the production of inflammatory factors. For inducing sleep deprivation, adult male mice were placed inside a water cage containing 15 platforms immersed in water up to 1 cm for 7 days. One day after sleep deprivation, dexmedetomidine at the respective dosage (5, 10, and 20 μg/kg) and α2-adrenoceptor antagonist atipamezole (250 μg/kg) were intraperitoneally injected into the mice, once per day for six days. The step-down avoidance task and the Morris water maze test were performed. Western blot analysis was performed to determine the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB), nuclear transcription factor-κB (NF-κB), inhibitor of κBα (IκBα), and ionized calcium binding adapter molecule I (Iba-1) in the hippocampus. Immunohistochemistry was performed for the determination of Ki-67 and glial fibrillary acidic protein (GFAP) expression in the hippocampal dentate gyrus. Dexmedetomidine ameliorated sleep deprivation-induced deterioration of short-term memory and spatial learning ability. Dexmedetomidine inhibited production of inflammatory mediators caused by sleep deprivation. Dexmedetomidine also prevented the decrease in BDNF, TrkB expression, and cell proliferation induced by sleep deprivation. Dexmedetomidine could be used to counteract the neuropathological effects of sleep deprivation.

Purpose: This study examined the effects of backward walking training with task orientation on the functional walking ability of children with cerebral palsy. Methods: This study was a single-blinded, randomized controlled trial with a crossover design conducted at a single rehabilitation facili ty with cross-over to the other intervention arm following a two-week break. For a total of 12 children with spastic hemiplegia cerebral palsy, the forward walking training group (n=6) underwent training three times a week for three weeks, 40 minutes a day, and the back ward walking training group (n=6) was also trained under the same conditions. To identify the functional walking ability, variables, such as the walking speed, stride length, and step length, were measured using a walk analyzer (OptoGait, Microgate S.r.l, Italy). Results: Both groups showed significant increases in walking speed, stride length, and step length (p

Sildenafil citrate, a potent and selective inhibitor of phosphodiesterase type-5, is used clinically to treat erectile dysfunction and pulmonary arterial hypertension. We investigated the effect of sildenafil citrate on brain central fatigue through serotonin (5-hydroxytryptamine, 5-HT) synthesis after exhaustive swimming exercise in rats. The rats in the sildenafil citrate-treated groups received sildenafil citrate orally once a day for 14 consecutive days at respective dosage. On the 14 days after starting experiment, each animal was submitted to swimming test with intensity equivalent to overload. The exhaustion was defined as a state in which coordinated movements did not return to the water surface for breathing within 10 sec. Immunohistochemistry for 5-HT, tryptophan hydroxylase (TPH), and western blot for serotonergic type 1A (5-HT1A) receptor and 5-HT transporter (5-HTT) were performed. Exhaustive swimming exercise increased 5-HT and TPH expressions in the dorsal raphe and sildenafil citrate suppressed 5-HT and TPH expressions in the exhaustive swimming exercise rats. Exhaustive swimming exercise increased 5-HT1A receptor and 5-HTT expressions in the dorsal raphe and sildenafil citrate suppressed 5-HT1A receptor and 5-HTT expressions in the exhaustive swimming exercise rats. The significant suppressing effect appeared in the 20-mg/kg sildenafil citrate. Sildenafil citrate might be proposed as a potential ergogenic aid through anticentral fatigue.

We examined whether exercise is associated with hippocampus-mediated improvement in insulin signaling and cell differentiation in the triple transgenic mouse model of Alzheimer disease (3xTg AD) murine model following exposure to 40-Hz light flickering and exercise. We subjected 12-month-old 3xTg AD mice to exercise and 40-Hz light flickering for 3 months. The exercise session was proceeded for 12 consecutive weeks with gradual increase of intensity. To investigate insulin signaling proteins, western blot was conducted to detect the ratio of phosphorylated insulin receptor β (p-IRβ)/total IRβ (t-IRβ), phosphorylated insulin receptor substrate 1 (p-IRS-1)/total IRS-1 (t-IRS-1), phosphorylated phosphatidylinositide-3-kinase (p-PI3K)/total PI3K (t-PI3K), phosphorylated 3-phosphoinositide dependent protein kinase-1 (p-PDK1)/total PDK-1 (t-PDK1), phosphorylated protein kinase B (p-Akt)/total-Akt (t-Akt), and phosphorylated glycogen synthase kinase 3 beta (p-GSK3β)/total GSK3β (t-GSK3β). Doublecortin immunohistochemistry was performed for assessing cell differentiation in the hippocampus. Treatments exerted a positive effect. The combination of exercise and 40-Hz light flickering exposure was the most effective treatment enhancing insulin signaling. Increased ratio of p-IRβ/t-IRβ, p-IRS-1/t-IRS-1, p-PI3K/t-PI3K, p-PDK1/t-PDK1, p-Akt/t-Akt, and p-GSK3β/t-GSK3β and enhanced cell differentiation were observed in the 3xTg AD with exercise under 40-Hz light flickering group. Our results indicate that exercise under 40-Hz light flickering most potently improved insulin signaling, thereby promoted cell differentiation.

Purpose: Wnt pathway is closely related to neurodevelopmental process associated with cognitive function. After administration of valproic acid to the pregnant mice, the effect of swimming exercise of pregnant mice on the memory, neuronal production, and apoptosis of pups was studied in relation with Wnt/β-catenin signaling pathway.Methods: On day 12 of pregnancy, mice were injected subcutaneously with 400-mg/kg valproic acid. The pregnant mice in the control with swimming exercise group and in the valproic acid injection with swimming exercise group were allowed for swimming for 30 minutes one time per a day, repeated 5 days per a week, during 3 weeks. Step-through avoidance task and Morris water maze task for memory function, immunohistochemistry for 5-bromo-2’-deoxyuridine (BrdU)-positive cells and western blot for brain-derived neurotrophic factor (BDNF), Wnt, β-catenin, Bcl-2 related X protein (Bax), B-cell lymphoma 2 (Bcl-2), cleaved caspase-3 were carried out.Results: Maternal swimming exercise during pregnancy improved memory function, increased BDNF expression, and neuronal proliferation in the valproic acid injected pups. Maternal swimming exercise during pregnancy suppressed Wnt expression and phosphorylation of β-catenin in the valproic acid injected pups. Maternal swimming exercise inhibited Bax and cleaved caspase-3 expression and increased Bcl-2 expression in the valproic acid injected pups.Conclusions: Maternal swimming exercise during pregnancy improved memory function by increasing cell proliferation and inhibiting apoptosis through Wnt/β-catenin signaling cascade activation in the valproic acid injected pups. Maternal swimming exercise during pregnancy may have a protective effect on factors that induce autism in the fetus.

The physiological processes of organisms in this rotating planet can adjust according to the time of day via built-in circadian clocks. However, more people are having different shift works, which can increase the risk of pathological conditions including altered reproductive function. Thus, circadian rhythm disturbance has become prevalent in the modern society. Specifically, epidemiological evidence has shown that shift-working women are at high risk of spontaneous abortions, irregular menstrual cycles, and low-birth-weight babies. The current study aimed to investigate the effects of circadian rhythm disturbances on the reproductive function of mice caused by dietary time shift, which is common among night-shift workers. According to the schedule of restricted feeding, the mice were classified into the free feeding, daytime feeding, and night feeding groups. The fertility indices of each group were then evaluated. Activity monitoring was performed to determine whether pregnancy delay might be attributed to mealtime shift. Moreover, the estrous cycle of female mice and the reproductive phenotype of male mice were investigated. Results showed that a 12-h mealtime shift significantly delayed successful conception, which could be attributed to a disrupted estrous cycle, in adult female mice.

The unfolded states of fibronectin (FN) subsequently induce the formation of the extracellular matrix (ECM) fibrillar network, which is necessary to generate new substitutive tissues. Here, we demonstrate that negatively charged small unilamellar vesicles (SUVs) qualify as candidates for FN delivery due to their remarkable effects on the autonomous binding and unfolding of FN, which leads to increased tissue regeneration. In vitro experiments revealed that the FN-SUV complex remarkably increased the attachment, differentiation, and migration of fibroblasts. The potential utilization of this complex in vivo to treat inflammatory colon diseases is also described based on results obtained for ameliorated conditions in rats with ulcerative colitis (UC) that had been treated with the FN-SUV complex. Our findings provide a new ECM-delivery platform for ECM-based therapeutic applications and suggest that properly designed SUVs could be an unprecedented FN-delivery system that is highly effective in treating UC and other diseases.

Traumatic brain injury (TBI) causes a variety of neuropathological manifestations including cognitive, emotional, physiological and psychological deficits. Physical exercise is known to ameliorate neurological impairments induced by various brain injuries. We investigated the effects of treadmill exercise on memory impairments due to TBI in relation to dopamine and D2 dopamine receptor. TBI was induced with an electromagnetic-controlled cortical impact device. The rats in the exercise groups were scheduled to run on a treadmill for 30 min once a day for 28 days after TBI induction. Then, step-down avoidance task, radial 8-arm maze test, immunohistochemistry for tyrosine hydroxylase (TH), and western blot for D2 dopamine receptor were performed. TBI impaired short-term and spatial learning memories. TBI decreased TH expressions in the prefrontal cortex (PFC), striatum, hippocampus dentate gyrus, and substantia nigra (SN). By contrast, the expressions of D2 dopamine receptor in the PFC, striatum, hippocampus, and SN were increased by TBI. Treadmill exercise alleviated the impairments of short-term and spatial learning memories observed in TBI rats. TH expression was decreased and D2 dopamine receptor expression was increased in TBI rats. Treadmill exercise enhanced TH expression and suppressed D2 dopamine receptor expression in TBI rats. TBI deteriorated short-term and spatial learning memories, in contrast, treadmill exercise alleviated the TBI-induced memory impairments by up-regulating dopamine level and down-regulating D2 dopamine receptor expression.

Nicotine withdrawal symptoms comprise insomnia, depression, anxiety, attention disorders, and increased craving. We evaluated the ameliorating effect of treadmill exercise on nicotine withdrawal symptoms. The rats in the nicotine withdrawal groups received subcutaneous injection with 6-mg/kg nicotine hydrogen tartrate salt for 17 days. And then, the injection of nicotine hydrogen tartrate salt was stopped next for 2 weeks. The rats in the exercise groups performed treadmill running once a day, 5 days per week, for 31 days. In the present results, activity was decreased and anxiety-like behavior was observed in the nicotine withdrawal rats. Treadmill running increased activity and ameliorated anxiety-like behavior in the nicotine-withdrawal rats. Expressions of tryptophan hydroxylase (TPH) and 5-hydroxytryptamine (5-HT) in the dorsal raphe were decreased in the nicotine withdrawal rats, in contrast, treadmill running increased TPH and 5-HT expressions. Impaired short-term memory and deteriorated spatial learning ability were observed in the nicotine withdrawal rats, in contrast, treadmill running ameliorated impairment of short-term memory and spatial learning ability. Expressions of brain-derived neurotrophic factor and tyrosine kinase B (TrkB) were decreased in the nicotine withdrawal rats, in contrast, treadmill running increased brain-derived neurotrophic factor and TrkB expressions. The numbers of the doublecortin (DCX)-positive cells and 5-bromo-2'-deoxyuridine (BrdU)-positive cells in the dentate gyrus were suppressed in the nicotine withdrawal rats, in contrast, treadmill running enhanced the numbers of DCX-positive cells and BrdU-positive cells. The present study demonstrate that treadmill exercise ameliorated nicotine withdrawal-induced anxiety, depression, and memory impairment.

Purpose Goserelin is a drug used for chemical castration. In a rat model, we investigated whether surgical and chemical castration affected memory ability through the protein kinase A (PKA)/cyclic adenosine monophosphate response elementbinding protein (CREB)/brain-derived neurotrophic factor (BDNF) and c-Raf/mitogen-activated protein kinases-extracellular signal-regulated kinases (MEK)/extracellular signal-regulated kinases (ERK) pathways in the hippocampus. Methods Orchiectomy was performed for surgical castration and goserelin acetate was subcutaneously transplanted into the anterior abdominal wall for chemical castration. Immunohistochemistry was done to quantify neurogenesis. To assess the involvement of the PKA/CREB/BDNF and c-Raf/MEK/ERK pathways in the memory process, western blots were used. Results The orchiectomy group and the goserelin group showed less neurogenesis and impaired short-term and spatial memory. Phosphorylation of PKA/CREB/BDNF and phosphorylation of c-Raf/MEK/ERK decreased in the orchiectomy and goserelin groups. Conclusion Short-term memory and spatial memory were affected by surgical and chemical castration via the PKA/CREB/BDNF and c-Raf/MEK/ERK signaling pathways.

Objectives The purpose of this study was to determine whether the cranial vertebral angle (CVA) and the range of motion (ROM) was different between participants with a forward head posture (FHP), with or without pain. Methods Forty-four participants who had FHP participated in this study. The FHP was assessed digitally by measuring a lateral view the CVA for each subject. A cervical ROM device measured the cervical ROM. The volunteers were allocated to either, with pain (n = 22), or without pain (n = 22) groups, and pain was evaluated using the Numeric Pain Rating Scale. Results The FHP in the pain group showed a significant difference in the CVA, and the cervical ROM in both flexion and extension, compared with those in the FHP without pain group (p < 0.05). Logistic regression analysis indicated that the occurrence of cervical area pain was higher amongst subjects who had a decreased CVA and flexion motion. Conclusion This study suggested that decreased CVA and cervical flexion range, were predictive factors for the occurrence of pain in the cervical region.

Purpose Sleep deprivation induces depressive symptoms. Dexmedetomidine is a α2-adrenoreceptor agonist and this drug possesses sedative, anxiolytic, analgesic, and anesthetic-sparing effect. In this study, the action of dexmedetomidine on sleep deprivation-induced depressive behaviors was investigated using mice. Methods For the inducing of sleep deprivation, the mice were placed inside a water cage containing 15 platforms and filled with water up to 1 cm below the platform surface for 7 days. One day after sleep deprivation, dexmedetomidine at the respective dosage (0.5, 1, and 2 μg/kg) was intraperitoneally treated into the mice, one time per a day during 6 days. Then, forced swimming test and tail suspension test were conducted. Immunohistochemistry for tyrosine hydroxylase (TH), 5-hydroxytryptamine (5-HT; serotonin), tryptophan hydroxylase (TPH) and western blot for D1 dopamine receptor were also performed. Results Sleep deprivation increased the immobility latency in the forced swimming test and tail suspension test. The expressions of TPH, 5-HT, and D1 dopamine receptor were decreased, whereas, TH expression was increased by sleep deprivation. Dexmedetomidine decreased the immobility latency and increased the expressions of TPH, 5-HT, and D1 dopamine receptor, whereas, HT expression was decreased by dexmedetomidine treatment. Conclusion In our results, dexmedetomidine alleviated sleep deprivation-induced depressive behaviors by increasing 5-HT synthesis and by decreasing dopamine production with up-regulation of D1 dopamine receptor.

Epilepsy is characterized by recurrent seizures and loss of neurons with abnormal rhythmic firing in the brains. In the present study, we investigated the effect of treadmill exercise on memory function in relation with cell proliferation and apoptosis in the hippocampus using pilocarpine-induced seizure rats. Epilepsy was initiated by intraperitoneal injection of pilocarpine hydrochloride. The rats in the exercise group were forced to run on a motorized treadmill for 30 min once a day for 2 weeks. In the present results, treadmill exercise alleviated short-term and spatial learning memory impairments in the epileptic rats. Treadmill exercise suppressed neuronal degeneration and enhanced neuronal maturation in the epileptic rats. Treadmill exercise suppressed cell proliferation and apoptosis in the epileptic rats. Treadmill exercise alleviated pilocarpine-induced memory impairments and suppressed neuronal loss in the hippocampus through down-regulation of apoptosis. These findings offer a possibility that treadmill exercise may provide a preventive or therapeutic value to the epilepsy-induced learning and memory impairments.

Il-Gyu Ko,1 Jun-Jang Jin,1 Lakkyong Hwang,1 Sang-Hoon Kim,1 Chang-Ju Kim,1 Kyu Yeoun Won,2 Yong Gil Na,3 Khae Hawn Kim,3 Su Jin Kim4 1Department of Physiology, College of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea; 2Department of Pathology, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, 05278, Korea; 3Department of Urology, Chungnam National University Sejong Hospital, College of Medicine, Chungnam National University, Sejong-si, 30099, Republic of Korea; 4Department of Urology, Yonsei University Wonju College of Medicine, Wonju, 26426, Republic of KoreaCorrespondence: Su Jin KimDepartment of Urology, Yonsei University Wonju College of Medicine, 20 Ilsanro, Wonju, Gangwon-do, 26426, Republic of KoreaTel +82-10-3287-0615Email hygeiasujin@naver.comBackground: Interstitial cystitis (IC) is a chronic disorder that indicates bladder-related pain or discomfort. Patients with IC often experience urination problems, such as urinary frequency and urgency, along with pain or discomfort in the bladder area. Therefore, new treatments based on IC etiology are needed. Polydeoxyribonucleotide (PDRN) is a biologic agonist of the adenosine A2A receptor, and PDRN has anti-inflammatory effect and inhibits apoptosis. In the current study, the effect of PDRN on cyclophosphamide-induced IC animal model was investigated using rats.Methodology: To induce the IC animal model, 75 mg/kg of cyclophosphamide was injected intraperitoneally once every 3 days for 10 days. The rats in the PDRN-treated groups were intraperitoneally injected with 0.5 mL physiological saline containing 8 mg/kg PDRN, once a day for 10 days after IC induction.Results: Induction of IC by cyclophosphamide injection caused voiding dysfunction, bladder edema, and histological damage. Cyclophosphamide injection increased secretion of pro-inflammatory cytokines and enhanced apoptosis. In contrast, PDRN treatment alleviated voiding dysfunction, bladder edema, and histological damage. Secretion of pro-inflammatory cytokines and expressions of apoptotic factors were suppressed by PDRN treatment. These changes indicate that treatment with PDRN improves voiding function by ultimately promoting the repair of damaged bladder tissue.Conclusion: The conclusion of this experiment suggests the possibility that PDRN could be used as an effective therapeutic agent for IC.Keywords: interstitial cystitis, adenosine A2A receptor, polydeoxyribonucleotide, voiding function, inflammation, apoptosis

Background: Alzheimer’s disease (AD) is a progressive degenerative brain disease and the primary cause of dementia. At an early stage, AD is generally characterized by memory impairment involving recent experiences owing to dysfunctions of the cortex and hippocampus. The lesion gradually spreads to the association cortex. Early amyloid-β (Aβ) deposition and tau protein expression result in a loss of synaptic function, mitochondrial damage, and increased cell death via microglia and astrocyte activation, which ultimately lead to cognitive decline. Exercise has been identified as a powerful tool for preventing AD-related neuroinflammation and cognitive decline, and light flickering at 40 Hz light flicker is known to stabilize gamma oscillations and reduce Aβ. Therefore, we investigated whether exercise under 40-Hz light flickering protects against cognitive decline based on analyses of neuroinflammation, mitochondrial function, and neuroplasticity in the hippocampus in a 3xTg AD mouse model.Methods: Using a 3xTg-AD model, 5-month-old mice were subjected to 12 weeks of exercise treatment and 40-Hz light flickering independently and in combination. Various factors, including spatial learning and memory, long-term memory, hippocampal Aβ, tau, neuroinflammation, pro-inflammatory cytokine expression, mitochondrial function, and neuroplasticity, were analyzed.Results: Aβ and tau proteins levels were significantly reduced in the early stage of AD, resulting in protection against cognitive decline by reduced neuroinflammation and pro-inflammatory cytokines, improved mitochondrial function, reduced apoptosis, and increased synapse-related protein expression. In particular, exercise under 40-Hz light flickering was more effective than exercise or 40-Hz light flickering alone, resulting in improvements in parameter values to levels in the non-transgenic aged-match control group.Conclusions: In this study, exercise under a special environment, such as 40-Hz light flickering, may exert a protective effect against cognitive decline. We detected synergistic effects of exercise and 40-Hz light flickering on pathological changes in the hippocampus in the early cognitive impairment of AD.

Background and objectives: Studies on the effects of an equine riding simulator (ERS) program on back pain, spinal alignment, and isokinetic moments in subjects with chronic low back pain (CLBP) remain limited. The purpose of this study was to analyze changes in elderly women with CLBP who participate in an ERS program. Materials and Methods: The 80 participants were all women aged 61&ndash, 84 years who were randomly assigned to either the control group (CON) or ERS group (ERSG). ERS exercise was performed for a duration of 12 weeks (three times each week). The degree of pain was measured using the Oswestry Disability Index and the visual analog scale. Body composition and spinal alignment were measured using bioelectrical impedance and raster stereography. The isokinetic moments of trunk extensor and flexor were measured before and after the training period. Results: The ERSG showed a significant decrease in back pain compared to the CON. There was a significant decrease in levels of fat in the ERSG, although no differences were shown in terms of muscle mass. However, there was an increased basal metabolic rate (BMR) in the ERSG. Spinal alignment in the ERSG significantly improved. The peak torques of the trunk extensor in the ERSG were also significantly increased. Conclusion: It can be inferred that the ERS exercise can decrease fat and improve the trunk extensor strength through increased BMR, leading to better spinal alignment and reducing back pain in elderly women with CLBP.

The purpose of this study is to determine whether moderate aerobic exercise training improves high-fat diet-induced alterations in mitochondrial function and structure in the skeletal muscle. Male 4-week-old C57BL/6 mice were randomly divided into four groups: control (CON), control plus exercise (CON + EX), high-fat diet (HFD), and high-fat diet plus exercise (HFD + EX). After obesity was induced by 20 weeks of 60% HFD, treadmill exercise training was performed at 13-16 m/min, 40-50 min/day, and 6 days/week for 12 weeks. Mitochondrial structure, function, and dynamics, and mitophagy were analyzed in the skeletal muscle fibers from the red gastrocnemius. Exercise training increased mitochondrial number and area and reduced high-fat diet-induced obesity and hyperglycemia. In addition, exercise training attenuated mitochondrial dysfunction in the permeabilized myofibers, indicating that HFD-induced decrease of mitochondrial O2 respiration and Ca2+ retention capacity and increase of mitochondrial H2 O2 emission were attenuated in the HFD + EX group compared to the HFD group. Exercise also ameliorated HFD-induced imbalance of mitochondrial fusion and fission, demonstrating that HFD-induced decrease in fusion protein levels was elevated, and increase in fission protein levels was reduced in the HFD + EX groups compared with the HFD group. Moreover, dysregulation of mitophagy induced by HFD was mitigated in the HFD + EX group, indicating a decrease in PINK1 protein level. Our findings demonstrated that moderate aerobic exercise training mitigated obesity-induced insulin resistance by improving mitochondrial function, and reversed obesity-induced mitochondrial structural damage by improving mitochondrial dynamics and mitophagy, suggesting that moderate aerobic exercise training may play a therapeutic role in protecting the skeletal muscle against mitochondrial impairments and insulin resistance induced by obesity.

Acute liver injury (ALI) causes life-threatening clinical problem, and its underlying etiology includes inflammation and apoptosis. An adenosine A2A receptor agonist, polydeoxyribonucleotide (PDRN), exhibits anti-inflammatory and anti-apoptotic effects by inhibiting the secretion of pro-inflammatory cytokines. In the current study, the protective effect of PDRN against carbon tetrachloride (CCl4)-induced ALI was investigated using mice. For the induction of ALI, mice received intraperitoneal injection of CCl4 twice over seven days. Mice from the PDRN-treated groups received an intraperitoneal injection of 200 &mu, L saline containing PDRN (8 mg/kg), once a day for seven days, starting on day 1 after the first CCl4 injection. In order to confirm that the action of PDRN occurs through the adenosine A2A receptor, 8 mg/kg 3,7-dimethyl-1-propargylxanthine (DMPX), an adenosine A2A receptor antagonist, was treated with PDRN. Administration of CCl4 impaired liver tissue and increased the liver index and histopathologic score. The expression of pro-inflammatory cytokines was increased, and apoptosis was induced by the administration of CCl4. Administration of CCl4 activated nuclear factor-kappa B (NF-&kappa, B) and facilitated phosphorylation of signaling factors in mitogen-activated protein kinase (MAPK). In contrast, PDRN treatment suppressed the secretion of pro-inflammatory cytokines and inhibited apoptosis. PDRN treatment inactivated NF-&kappa, B and suppressed phosphorylation of signaling factors in MAPK. As a result, liver index and histopathologic score were reduced by PDRN treatment. When PDRN was treated with DMPX, the anti-inflammatory and anti-apoptotic effect of PDRN disappeared. Therefore, PDRN can be used as an effective therapeutic agent for acute liver damage.