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Objective To examine the antidepressant effects of resveratrol (RSV),and its possible mechanism specialized on improving cognitive function.Methods Thirty-two C57BL/6J mice were randomly divided into four groups:Control,Model,Model+RSV and Model+NA+RSV groups.The mice were subjected corticosterone (20 mg/(kg · d)) intraperitoneal injection for 21 consecutive days except the control mice.From the 22nd to 42nd day,the mice in different groups received further treatment with vehicle/ RSV (400 mg/(kg · d),op)/NA (100 mg/(kg · d),ip)+RSV (400 mg/(kg · d),op).The sugar preference test,novel object recognition test,novel location recognition test and water maze test were applied to evaluate the cognitive effects of RSV on mice.Subsequently,the silence information regulation factor 1 (SIRT1),peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α),parvalbumin (PV) transcription and translation level were evaluated by RT-PCR and Western blotting.Results The sugar preference test showed that the depression model mediated by CORT injection was successfully established(F（1,30） =6,P=0.038).In in the novel object learning test,resveratrol significantly increased the proration on the frequency ((-0.20±0.37) vs (0.16±0.29))and duration((0.10±0.45) vs (0.62±0.29)) and decreased the proration on the distance((0.09±0.36) vs (0.55±0.27)).In the water maze test,resveratrol reduced the time((41±9)s;(26± 8) s) and distance ((295± 70) cm;(224±43) cm) to find the platform.All the results were accompanied with the increased expression of protein SIRT1 (F(3,29) =15.60,P＜0.01),PGC-1α(F(3,29)=7.51,P=0.0006) and PV (F(3,29) =17.87,P=0.0004).While pretreatment with nicotinamide,resveratrol could not rescue the cognitive impairment and could not reverse the iecreased expression level of protein SIRT1,PGC-1 α and PV.Conelusion Resveratrol can reverse the cognitive dysfunction of depressant mice,which may be achieved by activating the SIRT1/PGC-1α signaling pathway and increasing the transcription and protein expression of PV.
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<p><b>OBJECTIVE</b>To generate mice which are specific for peroxisomproliferator-activated receptor-γ coactivator-1(PGC-1α) knockout in the GABAergic interneuron.</p><p><b>METHODS</b>Conditional mice specific for PGC-1αwere introduced from the Jackson Laboratory, USA and initially inbred to obtain homozygote PGC-1αmice. The PGC-1αconditional mice were further crossed with Dlx5/6-Cre-IRES-EGFP transgenic mice to achieve specific knockout of PGC-1α in the GABAergic interneuron.</p><p><b>RESULTS</b>The offspring with specific knockout PGC-1α gene were successful for the generation of GABAergic interneuron, with the resulting genotype being PGC-1α.</p><p><b>CONCLUSION</b>The PGC-1αmice were obtained through a proper crossing strategy, which has provided a suitable platform for studying the function of PGC-1α in neuropsychiatric diseases.</p>
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Animals , Female , Humans , Male , Mice , Interneurons , Metabolism , Mice, Knockout , Neurodegenerative Diseases , Genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Genetics , gamma-Aminobutyric Acid , MetabolismABSTRACT
Objective To investigate the influence of aging on motor function,binding activity and protein expression level of striatum dopamine transporter(DAT)of rats. Methods Rolling-bar test was performed to assess motor function.Western blot and 131I-FP-β-CIT up-take ratio were used to evaluate DAT protein 1evel and striatum DAT binding activity respectively. Results There were an age-related decline of rolling-bar latency and striatum 131I-FP-β-CIT up-take ratio in rats older than6 months.There was a significant difference between 6-month-old rats and older rats(12-month-old rats,16-month-old rats,20-month-old rats),and rolling-bar latency was correlated with striatum 131I-FP-β-CIT up-take ratio(r=0.656,P＜0.01).There was no change in DAT protein 1evel during aging process. Conclusions The age-related decline of motor function of rats was correlated with the decreasing of striatum DAT binding activity.The synaptic membrane expression of striatum DAT may decrease in aged rats.
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Objective To observe the effect of mutant α-synuclein(A30P)in autophagic programmed cell death by transfected PC12 cells and explore its probable role and pathway in PD.Methods The definite PC12 cells which were transfected mutant α-synuclein(A30P)were constructed at first and MPP+,Rapamycin and Wortmanin were administrated to transfected PC12 cells with mutant α-synuclein. Not only the proliferative activity of cells was detected with MTT method but also the ultrastructttre changes of cells and expression of α-synuclein in different circumstance were observed by transmission electron microscopy(TEM),Western Blot and the level of SOD.Results (1)The expression of α-synuclein in groups A30P+Wortmannin and A30P+MPP+was higher than that in group A30P(P＜0.01), particularly.there was more significant expression of α-synuclein in group A30P+Wortmannin.The expression of α-synuclein in group A30P+Rapamycin was weaker than that in group A30P(P＜0.01); (2)The results showed that the SOD level(group A30P+MPP+:3 h:97.49±13.8;12 h:102.7±12.7; 24 h:101.5±11.8;48 h:104.3±12.4)was significantly decreased at various time points after MPP+ treatment compared that of group A30P(t=3.7721,P=0.0017).SOD level gradually increased in A30P +Rapamycin 12 h and showed significant difference at 24 h(121.2±13.0),48 h(124.3±14.1)and 72 h(127.7±13.7)after drug treatment compared with that in group A30P+Wortmannin(t:2.9746, P=0.0083);(3)Mutant α-synuclein(A30P)leading to PC12 cells death by means of autophagy involved α-synuclein accumulation,membrane lipid oxidation,and loss of plasma membrane integrity.Mutant α- synuclein(A30P)mediated the toxicity of MPP+.Rapamycin,an inducer of autophagy,reduced the aggregation of α-synuclein in transfected cells.Meanwhile,Wortmanin,an inhibitor of autophagy,promoted the aggregation of α-synuclein in transfected cells and induced cells to die.Conclusions The abnormal aggregation of α-synuclein induces autophagic programmed cell death in PC12 cells and mutant α-synuclein (A30P)mediates the toxicity of MPP+.Meanwhile,Rapamycin may reduce the aggregation of α-synuclein in transfeeted cells by activation of autophagic pathway.
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Objective To investigate the localization coexpression in situ of matrix metalloproteinase(MMP)-2,-8 and vascular endothelial growth factor(VEGF)in human atherosclerotic unstable plaques with monocytes,smooth muscle cells(SMCs)and endothelial cells(ECs).Methods The histopathologic changes of unstable human atherosclerotic plaques were observed by hematoxylin and eosin(HE)staining,and the localization coexpression of MMP-2,MMP-8 and VEGF in the unstable human atherosclerotic plaques were observed by double fluorescent immunochemistry technology and confocal microscopy.Results The human atherosclerotic plaques in 6 cases had typical histopathologic instability,which was classified as super-Ⅳ type unstable plaques.The MMP-2 coexpression was the most obvious in the smooth muscle cells of fibrous cap infiltrated by monocyts,and in the monocytes of shoulder of plaques,and more expression of MMP-2 in the microvascular endothelial cells at the edge of shoulder and lipid necrosis;MMP-8 coexpressed obviously with the monocytes in the fibrous cap and lipid cores of plaques,and next to coexpressing in the smooth muscle cells of fibrous cap,while coexpression in endothelial cells was very little;VEGF coexpression was significant in the proliferative microvascular endothelial cells of plaques;The fibrous cap,which consisted of the smooth muscle cells mainly,and the edge of lipid necrosis infiltrated by more monocyts,were over-expression areas of VEGF.Conclnsions MMP-2,-8 and VEGF can coexpress with monocytes,SMCs and ECs in unstable plaques,and the major expression areas are in the fibrous cap,shoulder and micro-vessel at the edge of lipid necrosis,which are infiltrated by monocytes.Moreover,the outer membrane of vessel is involved in the pathogenesis of atherosclerosis.
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Atherosclerosis is the most important pathological basis of ischemic cerebrovascular diseases. As an independent risk factor of atherosclerosis, fibrin(ogen) and its degradation products involve in the processes of the formation and development of atherosclerosis. This article reviews the relationship between fibrin(ogen) and/or its degradation products and atherosclerosis, and also introduces the development and application prospects for some specific motif antagonists of fibrin(ogen) in the treatment of atherosclerosis and ischemic cerebrovascular diseases.
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Objective To investigate the depression in stroke patients with broca aphasia.Methods Aphasia Depression Rating Scale (ADRS) and Zung's self-rating depression scale (SDS) were applied in patients on the first stroke with broca aphasia (Aphasia group,66 cases).The results were compared with stroke patients without aphasia(control group,66 cases).Results Compared to control group,the incidence of depression in Aphasia group was significantly higher(62.12% vs 25.76%,P