- Pharmacological investigation of 'HIM-CHX': A herbal combination in the experimental muscle wasting condition. [Journal Article]
- EGExp Gerontol 2019 Jul 15; :110663
- Muscle wasting diseases are gradually increasing with the increase in global life expectancy. This study was designed to evaluate the efficacy of HIM-CHX, a herbal combination of Boswellia serrata, C…
Muscle wasting diseases are gradually increasing with the increase in global life expectancy. This study was designed to evaluate the efficacy of HIM-CHX, a herbal combination of Boswellia serrata, Cissus quadrangularis, and Withania somnifera, on Sarcopenia. The effects of HIM-CHX on parameters such as muscle mass, grip strength, motor coordination, gait, locomotor activity, endurance were measured in rats. In addition to this, inflammatory cytokines, myokine and growth hormone levels were also evaluated. In the first experiment, HIM-CHX was administered orally to rats at a dose of 125, 250, and 500 mg/kg body weight for 12 weeks. At the end of the treatment period, muscle mass, grip strength, motor coordination and proinflammatory cytokines were evaluated. In the second experiment HIM-CHX was administered orally at a dose of 500 mg/kg body weight for 4 weeks and evaluated for gait analysis, locomotor activity, endurance and endogenous antioxidant activity. The animals treated with HIM-CHX showed a significant improvement in gastrocnemius muscle weight, carcass weight, gait, locomotor activity and endurance. HIM-CHX exerts its effect by reducing the levels of TNF-α, IL-6, and Myostatin while increasing the IGF-1 levels which are the typical biomarkers of muscle wasting. Furthermore, the study findings indicate that HIM-CHX has the potential to correct the pathophysiological changes associated with sarcopenia.
- The use of smartphone in measuring stance and gait patterns in patients with orthostatic tremor. [Journal Article]
- PlosPLoS One 2019; 14(7):e0220012
- Orthostatic tremor (OT) is a rare movement disorder characterized by a fast tremor (13-18 Hz) in the lower extremities during stance. Patients with OT typically complain of instability while standing…
Orthostatic tremor (OT) is a rare movement disorder characterized by a fast tremor (13-18 Hz) in the lower extremities during stance. Patients with OT typically complain of instability while standing/walking. However, due to the geographical limitation, the standing instability or gait problems in patients with OT cannot be assessed and monitored frequently. The increasing popularity of using smartphone-based accelerometers could be a solution to eliminate this limitation. This study examined the feasibility of using smartphone-based accelerometers to identify the changes in body movement in different standing and locomotor tasks. Twenty patients with OT and seven healthy controls were consented to participate in this study. Subjects stood with eyes open or eyes closed for 20 seconds. They also performed four different locomotor tasks (normal walking, tandem walk, walking on an elevated surface, and obstacle negotiation). When performed different locomotor tasks, patients with OT had a larger acceleration of body movement than controls in the medial-lateral direction (tandem walk: p = 0.026, walking on an elevated surface: p = 0.002, and stepping over the obstacle: p = 0.028). Patients with OT had smaller acceleration of body movement than controls while standing with eyes open in the vertical direction (p = 0.012), in the anterior-posterior direction (p = 0.013) and in the medial-lateral direction (p = 0.011). This study provides objective evidence of balance instability in patients with OT not only while standing but also during different challenging locomotor tasks by using smartphone-based accelerometers.
- A circuit-dependent ROS feedback loop mediates glutamate excitotoxicity to sculpt the Drosophila motor system. [Journal Article]
- EElife 2019 Jul 18; 8
- Overproduction of reactive oxygen species (ROS) is known to mediate glutamate excitotoxicity in neurological diseases. However, how ROS burdens can influence neural circuit integrity remains unclear.…
Overproduction of reactive oxygen species (ROS) is known to mediate glutamate excitotoxicity in neurological diseases. However, how ROS burdens can influence neural circuit integrity remains unclear. Here, we investigate the impact of excitotoxicity induced by depletion of Drosophila Eaat1, an astrocytic glutamate transporter, on locomotor central pattern generator (CPG) activity, neuromuscular junction architecture, and motor function. We show that glutamate excitotoxicity triggers a circuit-dependent ROS feedback loop to sculpt the motor system. Excitotoxicity initially elevates ROS to inactivate cholinergic interneurons, consequently changing CPG output activity to overexcite motor neurons and muscles. Remarkably, tonic motor neuron stimulation boosts muscular ROS, gradually dampening muscle contractility to feedback-enhance ROS accumulation in the CPG circuit and subsequently exacerbate circuit dysfunction. Ultimately, excess premotor excitation of motor neurons promotes ROS-activated stress signaling to alter neuromuscular junction architecture. Collectively, our results reveal that excitotoxicity-induced ROS can perturb motor system integrity by a circuit-dependent mechanism.
- Pequi enriched diets protect Drosophila melanogaster against paraquat-induced locomotor deficits and oxidative stress. [Journal Article]
- JTJ Toxicol Environ Health A 2019 Jul 18; :1-14
- The species Caryocar coriaceum Wittm (C. coriaceum), is popularly employed in northeast of Brazil for culinary purposes and in folk medicine. The oil from its fruit, deignated Pequi, is commonly used…
The species Caryocar coriaceum Wittm (C. coriaceum), is popularly employed in northeast of Brazil for culinary purposes and in folk medicine. The oil from its fruit, deignated Pequi, is commonly used to treat inflammatory problems, and its leaves to treat viral infections. However, comprehensive knowledge regarding the pharmacological properties attributed to these plant parts is still scarce. Thus, this study aimed to explore the in vivo antioxidant potential of aqueous extract of the leaves (AEL) and Pequi pulp oil (PPO) on the pro-oxidative effects induced by paraquat (PQ) using Drosophila melanogaster (D. melanogaster) as a model. These flies were fed with either standard or AEL and PPO supplemented diets prior to (pre-treatment for 7 days) or concomitantly (co-treatment for 5 days) with PQ. D. melanogaster administered PQ exhibited locomotor deficits and a higher rate of mortality. PQ induced significant changes in the antioxidant/oxidant status of D. melanogaster, including significant (1) increase in levels of reactive oxygen species (ROS) and lipid peroxidation; (2) elevation in the activity of antioxidant enzymes catalase (CAT) and glutathione-S-transferase (GST) and marked up-regulation in mRNA expression of stress-related genes for CAT, superoxide dismutase (SOD), thioredoxin reductase and Keap-1. Aside for mortality rates, AEL and PPO treatments reduced PQ-induced oxidative stress and motor impairments. No apparent evidence of toxicity was observed in D. melanogaster fed with AEL and PPO alone. Our findings provide evidence that AEL and PPO may confer protection against oxidant conditions by stimulating antioxidant responses.
- Nicotinic Acetylcholine Receptor Signaling in Neuroprotection: Shati/Nat8l and N-acetylaspartate (NAA) Have Important Roles in Regulating Nicotinic Acetylcholine Receptors in Neuronal and Psychiatric Diseases in Animal Models and Humans [BOOK]
- BOOKSpringer: Singapore
- Shati/Nat8l was originally isolated as a methamphetamine-related-molecule from the nucleus accumbens of mice. Since then, Shati/Nat8l has been characterized as an N-acetyltransferase-8-like protein (…
Shati/Nat8l was originally isolated as a methamphetamine-related-molecule from the nucleus accumbens of mice. Since then, Shati/Nat8l has been characterized as an N-acetyltransferase-8-like protein (Nat8l) that catalyzes N-acetylaspartate (NAA) synthesis from aspartate and acetyl-coenzyme A. It has been shown that elevated NAA levels detected by proton magnetic resonance spectroscopy (1H-MRS) brain imaging indicates increased neuronal activity. Our group produced Shati/Nat8l knock out mice (Shati/Nat8l KO mice), which exhibit hyper locomotion, anxiety behaviors, and social dysfunction. These mice have a high sensitivity to methamphetamine, as evidenced by their results in assessments of locomotor activity and conditioned place preference, as well as their elevated dopamine levels. We used an adeno-associated virus (AAV) vector containing Shati/Nat8l (AAV-Shati/Nat8l) to overexpress the protein in different brain regions such as the striatum and the nucleus accumbens, in order to investigate their involvement in methamphetamine-induced behavioral and pharmacological changes. We showed that overexpression of accumbal Shati/Nat8l attenuates methamphetamine-induced behaviors. Recent clinical studies have revealed further novel roles of Shati/Nat8l in psychiatric and neuronal diseases. We are just beginning to appreciate the various actions of this intriguing, recently discovered molecule in the central nervous system.
- Effects of a nutritional supplement in dogs affected by osteoarthritis. [Journal Article]
- VMVet Med Sci 2019 Jul 17
- Osteoarthritis is a form of chronic joint inflammation caused by the deterioration of the joint cartilage, accompanied by chronic pain, lameness and stiffness, particularly after prolonged activity. …
Osteoarthritis is a form of chronic joint inflammation caused by the deterioration of the joint cartilage, accompanied by chronic pain, lameness and stiffness, particularly after prolonged activity. Alternative treatments of canine osteoarthritis would be desirable and, recently nutraceuticals, have been proposed for this purpose. Twenty cross breed adult dogs affected by osteoarthritis were enrolled and equally divided into two groups (control vs. experimental). The nutritional supplement (Dynamopet srl, Verone, Italy) was administered for 90 days to the dogs of the experimental group in order to evaluate its metabolic and locomotor effects. All the clinical signs (lameness, pain on manipulation and palpation, range of motion and joint swelling) significantly (p < 0.01) improved during the trial as regards the experimental group. This group showed a significantly lower joint score than the control group (mean value 7.40 vs. 3.80). With regard to haematology, the mean corpuscular volume resulted significantly (p < 0.01) higher in the experimental group, i.e. alkaline phosphatase, cholesterol and triglycerides values decreased and were significantly (p < 0.01) lower than the control one, thus suggesting an improvement in bone remodelling and lipid metabolism. A decrease in the reactive oxygen metabolites and an increase in the biological antioxidant potential demonstrated an improvement in oxidative stress during the trial in the experimental group compare to the control group. Interleukins 6 decreased in the experimental group, while interleukins 10 resulted in the opposite trend. Moreover, the administration of up to 3 months of the studied supplement was well tolerated in the dogs and caused no adverse effects.
- Estimating Flight Style of Early Eocene Stem Palaeognath Bird Calciavis grandei (Lithornithidae). [Journal Article]
- ARAnat Rec (Hoboken) 2019 Jul 16
- Lithornithids are volant stem palaeognaths from the Paleocene-Eocene. Except for these taxa and the extant neotropical tinamous, all other known extinct and extant palaeognaths are flightless. Invest…
Lithornithids are volant stem palaeognaths from the Paleocene-Eocene. Except for these taxa and the extant neotropical tinamous, all other known extinct and extant palaeognaths are flightless. Investigation of properties of the lithornithid wing and its implications for inference of flight style informs understood locomotor diversity within Palaeognathae and may have implications for estimation of ancestral traits in the clade. Qualitative comparisons with their closest extant volant relatives, the burst-flying tinamous, previously revealed skeletal differences suggesting lithornithids were capable of sustained flight, but quantitative work on wing morphology have been lacking. Until comparatively recently, specimens of lithornithids preserving wing feather remains have been limited. Here, we reconstruct the wing of an exceptionally preserved specimen of the Early Eocene lithornithid Calciavis grandei and estimate body mass, wing surface area, and wing span. We then estimate flight parameters and compare our estimates with representatives from across Aves in a statistical framework. We predict that flight in C. grandei was likely marked by continuous flapping, and that lithornithids were capable of sustained flight and migratory behavior. Our results are consistent with previous hypotheses that the ancestor of extant Palaeognathae may also have been capable of sustained flight. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc.
- Re-examining the role of ventral tegmental area dopaminergic neurons in motor activity and reinforcement by chemogenetic and optogenetic manipulation in mice. [Journal Article]
- MBMetab Brain Dis 2019 Jul 16
- The precise contributions of ventral tegmental area (VTA) dopaminergic (DAergic) neurons to reward-related behaviors are a longstanding hot topic of debate. Whether the activity of VTA DAergic neuron…
The precise contributions of ventral tegmental area (VTA) dopaminergic (DAergic) neurons to reward-related behaviors are a longstanding hot topic of debate. Whether the activity of VTA DAergic neurons directly modulates rewarding behaviors remains uncertain. In the present study, we investigated the fundamental role of VTA DAergic neurons in reward-related movement and reinforcement by employing dopamine transporter (DAT)-Cre transgenic mice expressing hM3Dq, hM4Di or channelrhodopsin 2 (ChR2) in VTA DAergic neurons through Cre-inducible adeno-associated viral vector transfection. On the one hand, locomotion was tested in an open field to examine motor activity when VTA DAergic neurons were stimulated or inhibited by injection of the hM3Dq or hM4Di ligand clozapine-N-oxide (CNO), respectively. CNO injection to selectively activate or inhibit VTA DAergic neurons significantly increased or decreased locomotor activity, respectively, compared with vehicle injection, indicating that VTA DAergic neuron stimulation is directly involved in the regulation of motor activity. On the other hand, we used the optical intracranial self-stimulation (oICSS) model to investigate the causal link between reinforcement and VTA DAergic neurons. Active poking behavior but not inactive poking behavior was significantly escalated in a frequency- and pulse duration-dependent manner. In addition, microdialysis revealed that the concentration of dopamine (DA) in the nucleus accumbens (NAc) was enhanced by selective optogenetic activation of VTA DAergic neurons. Furthermore, systemic administration of a DA D1 receptor antagonist significantly decreased oICSS reinforcement. Our research profoundly demonstrates a direct regulatory role of VTA DAergic neurons in movement and reinforcement and provides meaningful guidance for the development of novel treatment strategies for neuropsychiatric diseases related to the malfunction of the reward system.
- Housing conditions modulate spontaneous physical activity, feeding behavior, aerobic running capacity and adiposity in C57BL/6J mice. [Journal Article]
- HBHorm Behav 2019 Jul 13
- There is evidence of reduced adiposity in rodents living in a large cages (LC) as compared to animals housed in small cages (SC). Because spontaneous physical activity (SPA) provides an important por…
There is evidence of reduced adiposity in rodents living in a large cages (LC) as compared to animals housed in small cages (SC). Because spontaneous physical activity (SPA) provides an important portion of the total daily energy expenditure, an increase of SPA in rodents kept in LC could explain their reduced body fat accumulation. The relationship between SPA and components of physical fitness (i.e. aerobic and anaerobic fitness and body leanness) has not been previously determined. We examined the effects of eight weeks of LC exposure on SPA, body composition, feeding behavior, as well as aerobic and anaerobic running capacity in adult C57BL/6J mice. Male mice were housed in cages of two different sizes for 8 weeks: a small (SC, n = 10) and large (LC n = 10) cages with 1320 cm2 and 4800 cm2 floor space, respectively. SPA was measured gravimetrically, and food and water intake were recorded daily. Mice had critical velocity (CV) and anaerobic running capacity (ARC) evaluated at the beginning, middle course (4th week) and at the end of study (8th week). Despite non-significant differences in each week LC-mice were more active than SC-mice by considering all SPA values obtained in the entire period of 8 weeks. The difference in SPA over the whole day was mainly due to light phase activity, but also due to activity at dark period (from 6 pm to 9 pm and from 5 am to 6 am). LC-mice also exhibited higher food and water intake over the entire 8-wk period. LC-mice had lower content of fat mass (% of the eviscerated carcass) than SC-mice (SC: 8.4 ± 0.4 vs LC: 6.3 ± 0.3, p < 0.05). LC-mice also exhibited reduced epididymal fat pads (% of body mass) compared to SC-mice (SC: 1.3 ± 0.1 vs LC: 0.9 ± 0.1, p < 0.05) and retroperitoneal fat pads (SC: 0.4 ± 0.05 vs LC: 0.2 ± 0.02, p < 0.05). The LC-group showed significantly higher critical velocity than SC-group at the fourth week (SC: 14.9 ± 0.6 m·min-1 vs LC: 18.0 ± 0.3 m·min-1, p < 0.05) and eighth week (SC: 17.1 ± 0.5 m·min-1 vs LC: 18.8 ± 0.6 m·min-1, p < 0.05). Our findings demonstrate that eight weeks of LC housing increases SPA of C57BL/6J mice, and this may lead to reduced fat accumulation as well as higher aerobic fitness. Importantly, our study implies that SC limits SPA, possibly generating experimental artifacts in long-term rodent studies.
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- The protective effect of cycloastragenol on aging mouse circadian rhythmic disorder induced by d-galactose. [Journal Article]
- JCJ Cell Biochem 2019 Jul 16
- Aging process in mammals is associated with a decline in amplitude and a long period of circadian behaviors which are regulated by a central circadian regulator in the suprachiasmatic nucleus (SCN) a…
Aging process in mammals is associated with a decline in amplitude and a long period of circadian behaviors which are regulated by a central circadian regulator in the suprachiasmatic nucleus (SCN) and local oscillators in peripheral tissues. It is unclear whether enhancing clock function can retard aging. Using fibroblasts expressing per2::lucSV and senescent cells, we revealed cycloastragenol (CAG), a natural aglycone derivative from astragaloside IV, as a clock amplitude enhancing small molecule. CAG could activate telomerase to antiaging, but no reports focused on its effects on circadian rhythm disorders in aging mice. Here we analyze the potential effects of CAG on d-galactose-induced aging mice on the circadian behavior and expression of clock genes. For this purpose, CAG (20 mg/kg orally), was administered daily to d-galactose (150 mg/kg, subcutaneous) mice model of aging for 6 weeks. An actogram analysis of free-running activity of these mice showed that CAG significantly enhances the locomotor activity. We further found that CAG increase expressions of per2 and bmal1 genes in liver and kidney of aging mouse. Furthermore, CAG enhanced clock protein BMAL1 and PER2 levels in aging mouse liver and SCN. Our results indicated that the CAG could restore the behavior of circadian rhythm in aging mice induced by d-galactose. These data of present study suggested that CAG could be used as a novel therapeutic strategy for the treatment of age-related circadian rhythm disruption.