Cui Y.-Q.,Key Laboratory of Neurodegenerative Diseases |
Zhang L.-J.,Key Laboratory of Neurodegenerative Diseases |
Zhang T.,Capital Medical University |
Luo D.-Z.,Key Laboratory of Neurodegenerative Diseases |
And 5 more authors.
Clinical and Experimental Pharmacology and Physiology | Year: 2010
Summary 1. Microglial activation plays an important role in the pathogenesis of neurodegenerative diseases by producing various pro-inflammatory cytokines. Microglia-derived nitric oxide (NO) is critical for the lipopolysaccharide (LPS)-induced selective loss of dopaminergic neurons. 2. Fucoidan is a sulphated polysaccharide extracted from brown seaweeds. It has a variety of biological actions, including anticoagulant, antiviral and anti-inflammatory effects. The aim of the present study was to investigate the effects of fucoidan on LPS-induced cellular activation in microglia and to evaluate the inhibitory mechanisms involved. 3. To investigate the effects of fucoidan on LPS-induced cellular activation in microglia, primary microglial cells were preincubated with fucoidan (31.25, 62.5 and 125 μg/mL) for 10 min, followed by stimulation with LPS (0.01 μg/mL). Then, cell shape and NO production were determined 24 h after LPS stimulation, whereas inducible nitric oxide synthase (iNOS) mRNA and protein expression were determined at 6 and 18 h after LPS stimulation, respectively. To evaluate the inhibitory mechanisms involved, mitogen-activated protein kinase (MAPK) activation was also evaluated. 4. Lipopolysaccharide transformed cells into an amoeboid shape, whereas 62.5 μg/mL fucoidan inhibited this activation. Moreover, 125 μg/mL fucoidan significantly inhibited microglial NO production to 75% of that in LPS-treated group and also significantly diminished the expression of iNOS mRNA and protein by nearly 50%. Fucoidan (125 μg/mL) also suppressed phosphorylation of p38 and extracellular signal-regulated kinase (ERK) by approximately 50%, but not that of c-Jun N-terminal kinase. 5. The results provide the first evidence that fucoidan has a potent inhibitory effect against LPS-induced NO production by microglia. The results also suggest that this inhibitory action of fucoidan involves suppression of p38 and ERK phosphorylation. © 2010 Blackwell Publishing Asia Pty Ltd.
Ping S.-H.,Kunming University of Science and Technology |
Yue F.,Key Laboratory of Neurodegenerative Diseases |
Wang C.-Y.,Kunming University of Science and Technology |
Luo Y.,Kunming University of Science and Technology |
And 2 more authors.
Journal of Animal and Veterinary Advances | Year: 2012
The objective was to examine the effect of Permeable Cryoprotectant Agents (CPAs) on sperm cryopreservation of tree shrew. Epididymal sperm were surgically harvested from captured wild male tree shrews and cryopreserved with Tes-Tris-Egg yolk based cryodiluent (TTE) containing either of the four CPAs, Dimethyl Sulfoxide (DMSO), Ethylene Glycol (EG), Propylene Glycol (PG) and Glycerol (Gly) at concentrations of 1, 3, 6 and 10%, respectively. Sperm motility, acrosome integrity and fertility were assessed. In Experiment 1, sperm equilibrated at 4oC in TTE containing 1, 3 and 6% DMSO, respectively showed similar motility to that in TTE without CPA (p>0.05). Following the increase of concentration of CPAs and equilibration time (30-90min), the other CPAs reduced sperm motility (p<0.05). In Experiment 2, sperm frozen in TTE containing 3% DMSO showed the highest post-thaw motility (p<0.05) and recovery rate of motility (p<0.05) among groups. In Experiment 3, there were no differences in the fertilization rate of oocytes and the proportion of tree shrews yielding fertilized oocytes inseminated with fresh and thawed sperm frozen in TTE containing 3% DMSO (p>0.05). In conclusion, among the permeable CPAs tested, DMSO provided the best cryoprotective ability for captured wild tree shrew epididymal sperm. © Medwell Journals, 2012.
Fang X.,Capital Medical University |
Fang X.,Beijing Geriatric Medical Research Center |
Fang X.,Key Laboratory of Neurodegenerative Diseases |
Fang X.,Beijing Municipal Key Laboratory of Clinical Epidemiology |
And 18 more authors.
Neuroepidemiology | Year: 2016
The Cardiovascular and Cognitive Health Study (CCHS-Beijing) is a population-based study of cardiovascular disease (CVD) and cognitive impairment in adults aged 55 and older in Beijing. The main aims of the study are to investigate the prevalence rates of CVD, asymptomatic atherosclerosis, and cognitive impairment, as well as validate the risk factors related to the onset and development of CVD, Alzheimer's disease (AD) and mild cognitive impairment (MCI). The study was designed to detect the traditional and new risk factors in this age group. Participants were recruited randomly from residential regions in the greater Beijing municipality area based on the average levels of development in Beijing, China in 2012 (based on socioeconomic, demographic, and geographical characteristics). Thorough physical and laboratory examination were performed at baseline (also the cross-sectional survey) to identify the risk factors such as hypertension, dyslipidemia, diabetes, as well as newly defined risk factors like elevated homocysteine, high sensitivity C-reactive protein, and urine micro-albumin. Subclinical disease of the cerebral vasculature included atherosclerosis of carotid arteries, intracranial arteries, and retinal vessels. Subclinical cardiac diseases included left ventricular enlargement, arrhythmias, chamber hypertrophy and myocardial ischemia. Blood pressure was documented using the ankle-arm method. In addition, neuropsychological assessments were performed for all subjects aged 65 and above. Baseline evaluation began during the period August 2013 to December 2014. Follow-up examination will occur in 5 years. The initial and recurrent CVD, AD and MCI events will be verified and validated during the follow-up period. © 2016 S. Karger AG, Basel.
Yue F.,Capital Medical University |
Yue F.,Key Laboratory of Neurodegenerative Diseases |
Zeng S.,Guilin Medical College |
Wu D.,Capital Medical University |
And 5 more authors.
Journal of Neural Transmission | Year: 2012
Advanced human aging is associated with progressive declines of motor function and a risk factor for Parkinson's disease, which mainly involves central nigrostriatal dopaminergic system. The present study investigated age-related changes in motor behaviors and alterations of the number of nigrostriatal dopaminergic terminals in non-human primates. A total of 30 cynomolgus monkeys (Macaca fascicularis) of age 3.5-15.5 years were studied. Motor behaviors including upper limb movement time and the amount of overall home cage activity were quantitatively assessed using a modified movement assessment panel and a newly developed webcam-based monitoring system. The function of the dopaminergic system was semi-quantitatively measured by 99mTc-TRODAT-1 uptake rates, a dopamine transporter (DAT) specific radiopharmaceutical with SPECT imaging. The results showed a significant decline in motor behaviors associated with aging which were significantly correlated with age-related decreases of 99mTc-TRODAT-1 uptake. A further partial correlation analysis independent of age indicated that age contributed to the relationship between striatal DAT levels and motor behaviors. Our results indicate that normal aging-related dopamine physiology influences certain aspects of motor behaviors and suggest that aging-associated dysfunction in the nigrostriatal dopaminergic system may be an important factor contributing to the decline of motor behaviors in aging cynomolgus monkeys. © 2012 Springer-Verlag.
Zhao Y.,Capital Medical University |
Zhao Y.,Beijing Geriatric Medical Research Center |
Zhao Y.,Key Laboratory of Neurodegenerative Diseases |
Zhao Y.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases |
And 24 more authors.
Stroke | Year: 2014
BACKGROUND AND PURPOSE - : Zinc has been reported to possess both neurotoxic and neuroprotective capabilities. The effects of elevated intracellular zinc accumulation following transient focal cerebral ischemia remain to be fully elucidated. Here, we investigated whether removing zinc with the membrane-permeable zinc chelator, N,N,N′,N′-tetrakis(2- pyridylmethyl)ethylenediamine (TPEN), would decrease the intracellular levels of zinc in the ischemic tissue, leading to reduced brain damage and improved neurological outcomes. METHODS - : Rats were pretreated with TPEN or vehicle before or after a 90-minute middle cerebral artery occlusion. Cerebral infarct volume, neurological functions, neuronal apoptosis, poly(ADP-ribose) polymerase activity, and cytosolic labile zinc were assessed after ischemia and reperfusion. RESULTS - : Cerebral ischemia caused a dramatic cytosolic labile zinc accumulation in the ischemic tissue, which was decreased markedly by TPEN (15 mg/kg) pretreatment. Chelating zinc lead to reduced infarct volume compared with vehicle-treated middle cerebral artery occlusion rats, accompanied by much improved neurological assessment and motor function, which were sustained for 14 days after reperfusion. We also determined that reducing zinc accumulation rescued neurons from ischemia-induced apoptotic death by reducing poly(ADP-ribose) polymerase-1 activation. CONCLUSIONS - : Ischemia-induced high accumulation of intracellular zinc significantly contributed to ischemic brain damage through promotion of neuronal apoptotic death. Removing zinc may be an effective and novel approach to reduce ischemic brain injury. © 2014 American Heart Association, Inc.