Neuroprotective effect of low-dose paracetamol treatment against cognitive dysfunction in d-galactose-induced aging mice.

Background: Aging is closely associated to several deleterious conditions and cognitive impairment. Administration of low-dose paracetamol (APAP) has previously been reported to improve cognitive performance in both human and animal studies. However, the altered cognitive effects of low-dose APAP treatment in the aging brain have not been elucidated. Objectives: The purpose of this study was to determine whether low-dose APAP treatment improves cognitive dysfunction in a d-galactose (d-gal)-induced aging model. Materials and methods: APAP (15 and 50 mg/kg p.o.) and vitamin E (Vit E 100 mg/kg p.o.) were administered once daily to d-gal-injected mice (200 mg/kg s.c.) for 6 weeks. The elevated plus maze (EPM), open field, novel object recognition (NOR), and Morris water maze (MWM) tests, respectively, were used to measure altered neurobehavioral functions, including anxiety-like behavior and exploratory locomotor activity, as well as learning and memory performance. The gene transcription of brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling in brain tissues was evaluated by real-time polymerase chain reaction. Results: Compared to the control, d-gal significantly decreased exploratory locomotor activity and NOR and MWM performance but did not significantly change the activity in the EPM test. However, APAP50 and Vit E significantly reversed the effects of d-gal injection on exploratory locomotor activity. In addition, low-dose APAP (15 and 50 mg/kg) and Vit E significantly improved the reduction in NOR and MWM performance induced by d-gal. Real-time polymerase chain reaction analysis revealed that the mRNA expression of BDNF, neurotrophic tyrosine receptor kinase (NTRK), which is the gene coding TrkB receptor, and cAMP response element-binding protein (CREB) was significantly decreased in the frontal cortex and hippocampus of the d-gal mice. However, APAP50 and Vit E significantly increased BDNF and NTRK mRNA expression in both the frontal cortex and the hippocampus. A lower dose of APAP (15 mg/kg) significantly elevated the mRNA expression of NTRK, but only in the hippocampus. Moreover, APAP50 significantly increased CREB mRNA expression in the frontal cortex and hippocampus. Conclusion: Low-dose APAP treatment has a neuroprotective effect on cognitive dysfunction in the d-gal aging model, and the underlying molecular mechanisms depend on the activation of BDNF/TrkB signaling.

Effects of an online yoga program on anthropometric parameters among overweight female students during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) outbreak is a public health concern. However, stay-at-home regulations to prevent disease spread increased sedentary behavior with unintended adverse outcomes. Overweight is a major global health issue, and standard treatments have a poor track record of long-term effectiveness. The purpose of this study was to evaluate how online yoga affected participants who were overweight in terms of anthropometric measurements. The study, which was designed as a experimental study, enrolled sixty overweight adolescents. The participants were divided into two groups: a control group (n = 30) and an intervention group (n = 30) who performed an online yoga home exercise program comprising basic yoga practice with 15 poses and minimal rest periods on Monday Wednesday and Friday, from 5.00 to 5.45 pm for 12 weeks. The intensity of the exercise was 65-75 percent of maximum heart rate (MHR). Anthropometric parameters, including body weight (BW), body mass index (BMI), body circumference measurements (BCM), and resting heart rate (RHR) were assessed. All parameters were measured at weeks 0, 8, and 12. Within group and between group comparisons were performed. The results revealed improved BW, BMI, BCM, and RHR in the intervention group; the median BW and BMI of the intervention group was significantly decreased at week 12, and the BCM of the intervention group showed a significant decrease in the chest, waist, hip, and thigh. This declining trend started from week 8. This 12-week online yoga program decreased BW, BMI, BCM, and RHR, which indicates that practicing yoga at home is effective on anthropometric parameters and may be an alternative therapy for health promotion and controlling body weight during the COVID-19 pandemic. However, an appropriate and continuous exercise program must be followed.

The Effects of Exercise on Aging-Induced Exaggerated Cytokine Responses: An Interdisciplinary Discussion.

Aging is generally known to be associated with dynamic biological changes, physiological dysfunction, and environmental and psychological decline. Several studies have suggested that aging is associated with increased inflammatory cytokines, causing several diseases. However, the effect of exercise on aging has been less delineated, and the relationships between cytokine activation, aging, and exercise also need further study. Here, we discuss some ideas about the effect of exercise on aging-induced exaggerated cytokine responses and discuss the possible roles of the aging-induced exaggerated cytokine response following exercise. Evidence from these findings suggests that exercise is a beneficially applicable model to use in studies on the mechanisms underlying the age-associated gradated cytokine response, and these results may provide guidelines for health professionals with diverse backgrounds.

Involvement of N-type Ca2+ channel in microglial activation and its implications to aging-induced exaggerated cytokine response.

Voltage-dependent calcium channel (VDCC) is generally believed to be active only in excitable cells. However, we have reported recently that N-type VDCC (Cav2.2) could become functional in non-excitable cells under pathological conditions. In the present study, we show that Cav2.2 channels are also functional in physiological microglial activation process. By using a mouse microglial cell line (MG6), we examined the effects of a Cav2.2 blocker on the activation of MG6 cells, when treated with lipopolysaccharide (LPS) / interferon γ (IFNγ) or with interleukin-4 (IL-4). As a result, blocking the activation of Cav2.2 enhanced so-called alternative activation process of microglia (transition to neuroprotective M2 microglia) without changing the efficacy of the transition to neuroinflammatory M1 microglia. This enhanced M2 transition involved the activation of a transcription factor hypoxia inducible factor 2 (HIF-2), since a specific blocker of HIF-2 completely abolished this enhancement. We then examined whether Cav2.2 activation was involved in aging-related neuroinflammation. Using primary culture of microglia, we found that the efficacy of microglial M1 transition was enhanced but that M2 transition was reduced by aging, in agreement with a general notion that aging induces enhanced neuroinflammation. Finally, we show here that the moderate blockade of Cav2.2 expression in microglia restores this age-dependent reduction of microglial M2 transition and reduces the aging-induced exaggerated cytokine response, as revealed by a fast recovery from depressive-like behaviors in microglia-specific Cav2.2 deficient mice. These results suggest a critical role for microglial Cav2.2 channel in the aging-related neuroinflammation.

Blockade of microglial Cav1.2 Ca2+ channel exacerbates the symptoms in a Parkinson's disease model.

Cav1.2 channels are an L-type voltage-dependent Ca2+ channel, which is specifically blocked by calcium antagonists. Voltage-dependent Ca2+ channels are generally considered to be functional only in excitable cells like neurons and muscle cells, but recently they have been reported to also be functional in non-excitable cells like microglia, which are key players in the innate immune system and have been shown to be involved in the pathophysiology of Parkinson's disease. Here, we show that Cav1.2 channels are expressed in microglia, and that calcium antagonists enhanced the neuroinflammatory M1 transition and inhibited neuroprotective M2 transition of microglia in vitro. Moreover, intensive degeneration of dopaminergic neurons and accompanying behavioural deficits were observed in microglia-specific Cav1.2 knockdown mice intoxicated with MPTP, a neurotoxin that induces Parkinson's disease-like symptoms, suggesting detrimental effects of microglial Cav1.2 blockade on Parkinson's disease. Therefore, microglial Cav1.2 channel may have neuroprotective roles under physiological conditions and may also contribute to recovery from disease conditions.