ABSTRACT
Huntington's disease (HD) is a neurodegenerative disease caused by a polyglutamine expansion in the huntingtin (Htt) protein. Mutant Htt causes synaptic transmission dysfunctions by interfering in the expression of synaptic proteins, leading to early HD symptoms. Synaptic vesicle proteins 2 (SV2s), a family of synaptic vesicle proteins including 3 members, SV2A, SV2B, and SV2C, plays important roles in synaptic physiology. Here, we investigated whether the expression of SV2s is affected by mutant Htt in the brains of HD transgenic (TG) mice and Neuro2a mouse neuroblastoma cells (N2a cells) expressing mutant Htt. Western blot analysis showed that the protein levels of SV2A and SV2B were not significantly changed in the brains of HD TG mice expressing mutant Htt with 82 glutamine repeats. However, in the TG mouse brain there was a dramatic decrease in the protein level of SV2C, which has a restricted distribution pattern in regions particularly vulnerable in HD. Immunostaining revealed that the immunoreactivity of SV2C was progressively weakened in the basal ganglia and hippocampus of TG mice. RT-PCR demonstrated that the mRNA level of SV2C progressively declined in the TG mouse brain without detectable changes in the mRNA levels of SV2A and SV2B, indicating that mutant Htt selectively inhibits the transcriptional expression of SV2C. Furthermore, we found that only SV2C expression was progressively inhibited in N2a cells expressing a mutant Htt containing 120 glutamine repeats. These findings suggest that the synaptic dysfunction in HD results from the mutant Htt-mediated inhibition of SV2C transcriptional expression. These data also imply that the restricted distribution and decreased expression of SV2C contribute to the brain region-selective pathology of HD.
Subject(s)
Animals , Mice , Aging , Metabolism , Brain , Metabolism , Pathology , Cell Line, Tumor , Gene Expression , Physiology , Huntingtin Protein , Genetics , Metabolism , Membrane Glycoproteins , Metabolism , Mice, Transgenic , Mutation , Nerve Tissue Proteins , Metabolism , RNA, Messenger , Metabolism , Transcription, Genetic , PhysiologyABSTRACT
Objective To investigate the expression and effects of endothelin-1 (ET-1) in cerebral vessels of scalded rats. MethodHistological method was used to observe the alteration of histological structure of basilar artery in 8 scalded rats. Reverse transcription polymerase chain reaction(RT-PCR) was performed to examine expression of ET-1 mRNA;Western blotting to analyse expression of endothelin-1;radioimmunoassay to measure ET-1 levels;R3espectively, of cerebral basilar artery in 48 scalded rats. ResultVascular pathohistological changes were observed in cerebral basilar artery after rats were scalded;ET-1, ET-1 mRNA expression and ET-1 levels of basilar artery in scald 6 hours, 12 hours and 24 hours group were obviously higher than that of control group. Conclusion Scald may cause an increases of ET-1 expression in basilar artery, and elevated ET-1 expression may relate to the pathogenesis of cerebral vascular injury in scalded rats.
ABSTRACT
Objective To study the risk factors for stroke in young adults.Methods 178 young adults aged from 18～45 years with stroke were selected from patients admitted in our hospital,including 106 patients with cerebral infarction and 72 patients with cerebral hemorrhage.And then risk factors for stroke in all the patients were studied.Results Hypertension,the habit of smoking,excessive drinking and family history were the first few risk factors of the main risk factors for stroke in young adults,and overweight and hyperlipidemia accounted for large percentage,too.But diabetes mellitus,heart disease and TIA were not main risk factors for stroke in young adults.Conclusion Antihypertensive treatment is important work in primary prevention of stroke in young adults.Attention for healthy life style and special education of health knowledge for stroke in young adults should be carried out to decrease the risk of stroke in young adults.