An enriched environment protects dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced neuronal injury, but the underlying mechanism for this is not clear. Growth associated protein-43...An enriched environment protects dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced neuronal injury, but the underlying mechanism for this is not clear. Growth associated protein-43(GAP-43) is closely associated with neurite outgrowth and axon regeneration during neural development. We speculate that an enriched environment can reduce damage to dopaminergic neurons by affecting the expression of GAP-43. This study is designed to test this hypothesis. Three-month-old female senescence-accelerated mouse prone 8(SAMP8) mice were housed for 3 months in an enriched environment or a standard environment. These mice were then subcutaneously injected in the abdomen with 14 mg/kg MPTP four times at 2-hour intervals. Morris water maze testing demonstrated that learning and memory abilities were better in the enriched environment group than in the standard environment group. Reverse-transcription polymerase chain reaction, immunohistochemistry and western blot assays showed that m RNA and protein levels of GAP-43 in the substantia nigra were higher after MPTP application in the enriched environment group compared with the standard environment group. These findings indicate that an enriched environment can increase GAP-43 expression in SAMP8 mice. The upregulation of GAP-43 may be a mechanism by which an enriched environment protects against MPTP-induced neuronal damage.展开更多
Objective: To investigate the preventive treatment effects of electroacupuncture(EA) on cognitive changes and brain damage in senescence-accelerated mouse prone 8(SAMP8) mice. Methods: The 5-month-old male SAMP8...Objective: To investigate the preventive treatment effects of electroacupuncture(EA) on cognitive changes and brain damage in senescence-accelerated mouse prone 8(SAMP8) mice. Methods: The 5-month-old male SAMP8 and age-matched homologous normal aging mice(SAMR1) were adopted in this study. EA stimulation at Baihui(GV 20) and Yintang(EX-HN 3) was performed every other day for 12 weeks, 4 weeks as a course. Morris water maze test and Nissl-stained with cresyl violet were used for cognitive impairments evaluation and brain morphometric analysis. Amyloid-β(Aβ) expression in hippocampus and parietal cortex was detected by immunohistochemistry, and apoptosis was observed by TUNEL staining. Results: After 3 courses of EA preventive treatment, the escape latencies of 8-month-old SAMP8 mice in EA group were significantly shortened than those of un-pretreated SAMP8 mice. Compared with SAMR1 mice, extensive neuronal changes were visualized in the CA1 area of hippocampus in SAMP8 mice, while these pathological changes and attenuate cell loss in hippocampal CA1 area of SAMP8 mice markedly reduced after EA preventive treatment. Furthermore, Aβ expression in hippocampus and parietal cortex of SAMP8 mice decreased significantly after EA treatment, and neuronal apoptosis decreased as well. Conclusion: EA preventive treatment at GV 20 and EX-HN 3 might improve cognitive deficits and neuropathological changes in SAMP8 mice, which might be, at least in part, due to the effects of reducing brain neuronal damage, decreasing neuronal apoptosis and inhibiting Aβ-containing aggregates.展开更多
3,4-O-异亚丙基莽草酸(ISA)是从木兰科植物八角茴香(Illicium verum Hook.Fil.)中提取的有效成分莽草酸的衍生物,具有抗炎、抗血栓和抗缺血性脑损伤等作用,关于其对于阿尔茨海默病的作用尚不清楚.本研究发现,ISA可显著改善SAMP-8快速老...3,4-O-异亚丙基莽草酸(ISA)是从木兰科植物八角茴香(Illicium verum Hook.Fil.)中提取的有效成分莽草酸的衍生物,具有抗炎、抗血栓和抗缺血性脑损伤等作用,关于其对于阿尔茨海默病的作用尚不清楚.本研究发现,ISA可显著改善SAMP-8快速老化小鼠(Mus musculus)的空间学习记忆能力,降低脑皮层IL-1,IL-6,TNF-?和Caspase-3水平,降低海马区p-Tau蛋白表达,升高海马区沉默信息调节因子2同源蛋白1(SIRT1)蛋白表达.本研究表明,ISA可通过抑制过度神经炎性反应、增加SIRT1表达,降低Tau蛋白磷酸化,改善阿尔茨海默病造成的认知功能损伤.展开更多
BACKGROUND: The pharmacological actions of Panax notoginseng saponins (PNS) lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheime...BACKGROUND: The pharmacological actions of Panax notoginseng saponins (PNS) lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheimer's disease. OBJECTIVE: Using the Morris water maze, immunohistochemistry, real-time PCR and RT-PCR, this study aimed to measure improvement in spatial learning, memory, expression of amyloid precursor protein (App) and β -amyloid (A β ), to investigate the mechanism of action of PNS in the treatment of AD in the senescence accelerated mouse-prone 8 (SAMP8) and compare the effects with huperzine A. DESIGN, TIME AND SETTING: A completely randomized grouping design, controlled animal experiment was performed in the Center for Research & Development of New Drugs, Guangxi Traditional Chinese Medical University from July 2005 to April 2007. MATERIALS: Sixty male SAMP8 mice, aged 3 months, purchased from Tianjin Chinese Traditional Medical University of China, were divided into four groups: PNS high-dosage group, PNS low-dosage group, huperzine A group and control group. PNS was provided by Weihe Pharmaceutical Co., Ltd. (batch No.: Z53021485, Yuxi, Yunan Province, China). Huperzine A was provided by Zhenyuan Pharmaceutical Co., Ltd. (batch No.: 20040801, Zhejiang, China). METHODS: The high-dosage group and low-dosage group were treated with 93.50 and 23.38 mg/kg PNS respectively per day and the huperzine A group was treated with 0.038 6 mg/kg huperzine A per day, all by intragastric administration, for 8 consecutive weeks. The same volume of double distilled water was given to the control group. MAIN OUTCOME MEASURES: After drug administration, learning and memory abilities were assessed by place navigation and spatial probe tests. The recording indices consisted of escape latency (time-to-platform), and the percentage of swimming time spent in each quadrant. The number of A β 1-40, A β 1-42 and App immunopositive neurons in the brains of SAMP8 mice w展开更多
基金supported by a grant from the Health Department of Hebei Province of China,No.20120056,20140314the Funding Project for Introduced Abroad Study Personnel of Hebei Province of China,No.C2011003039
文摘An enriched environment protects dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced neuronal injury, but the underlying mechanism for this is not clear. Growth associated protein-43(GAP-43) is closely associated with neurite outgrowth and axon regeneration during neural development. We speculate that an enriched environment can reduce damage to dopaminergic neurons by affecting the expression of GAP-43. This study is designed to test this hypothesis. Three-month-old female senescence-accelerated mouse prone 8(SAMP8) mice were housed for 3 months in an enriched environment or a standard environment. These mice were then subcutaneously injected in the abdomen with 14 mg/kg MPTP four times at 2-hour intervals. Morris water maze testing demonstrated that learning and memory abilities were better in the enriched environment group than in the standard environment group. Reverse-transcription polymerase chain reaction, immunohistochemistry and western blot assays showed that m RNA and protein levels of GAP-43 in the substantia nigra were higher after MPTP application in the enriched environment group compared with the standard environment group. These findings indicate that an enriched environment can increase GAP-43 expression in SAMP8 mice. The upregulation of GAP-43 may be a mechanism by which an enriched environment protects against MPTP-induced neuronal damage.
基金Supported by the National Natureal Science Foundation of China(No.30701121)
文摘Objective: To investigate the preventive treatment effects of electroacupuncture(EA) on cognitive changes and brain damage in senescence-accelerated mouse prone 8(SAMP8) mice. Methods: The 5-month-old male SAMP8 and age-matched homologous normal aging mice(SAMR1) were adopted in this study. EA stimulation at Baihui(GV 20) and Yintang(EX-HN 3) was performed every other day for 12 weeks, 4 weeks as a course. Morris water maze test and Nissl-stained with cresyl violet were used for cognitive impairments evaluation and brain morphometric analysis. Amyloid-β(Aβ) expression in hippocampus and parietal cortex was detected by immunohistochemistry, and apoptosis was observed by TUNEL staining. Results: After 3 courses of EA preventive treatment, the escape latencies of 8-month-old SAMP8 mice in EA group were significantly shortened than those of un-pretreated SAMP8 mice. Compared with SAMR1 mice, extensive neuronal changes were visualized in the CA1 area of hippocampus in SAMP8 mice, while these pathological changes and attenuate cell loss in hippocampal CA1 area of SAMP8 mice markedly reduced after EA preventive treatment. Furthermore, Aβ expression in hippocampus and parietal cortex of SAMP8 mice decreased significantly after EA treatment, and neuronal apoptosis decreased as well. Conclusion: EA preventive treatment at GV 20 and EX-HN 3 might improve cognitive deficits and neuropathological changes in SAMP8 mice, which might be, at least in part, due to the effects of reducing brain neuronal damage, decreasing neuronal apoptosis and inhibiting Aβ-containing aggregates.
文摘3,4-O-异亚丙基莽草酸(ISA)是从木兰科植物八角茴香(Illicium verum Hook.Fil.)中提取的有效成分莽草酸的衍生物,具有抗炎、抗血栓和抗缺血性脑损伤等作用,关于其对于阿尔茨海默病的作用尚不清楚.本研究发现,ISA可显著改善SAMP-8快速老化小鼠(Mus musculus)的空间学习记忆能力,降低脑皮层IL-1,IL-6,TNF-?和Caspase-3水平,降低海马区p-Tau蛋白表达,升高海马区沉默信息调节因子2同源蛋白1(SIRT1)蛋白表达.本研究表明,ISA可通过抑制过度神经炎性反应、增加SIRT1表达,降低Tau蛋白磷酸化,改善阿尔茨海默病造成的认知功能损伤.
基金the National Natural Science Foundation of China, No: 30560189
文摘BACKGROUND: The pharmacological actions of Panax notoginseng saponins (PNS) lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheimer's disease. OBJECTIVE: Using the Morris water maze, immunohistochemistry, real-time PCR and RT-PCR, this study aimed to measure improvement in spatial learning, memory, expression of amyloid precursor protein (App) and β -amyloid (A β ), to investigate the mechanism of action of PNS in the treatment of AD in the senescence accelerated mouse-prone 8 (SAMP8) and compare the effects with huperzine A. DESIGN, TIME AND SETTING: A completely randomized grouping design, controlled animal experiment was performed in the Center for Research & Development of New Drugs, Guangxi Traditional Chinese Medical University from July 2005 to April 2007. MATERIALS: Sixty male SAMP8 mice, aged 3 months, purchased from Tianjin Chinese Traditional Medical University of China, were divided into four groups: PNS high-dosage group, PNS low-dosage group, huperzine A group and control group. PNS was provided by Weihe Pharmaceutical Co., Ltd. (batch No.: Z53021485, Yuxi, Yunan Province, China). Huperzine A was provided by Zhenyuan Pharmaceutical Co., Ltd. (batch No.: 20040801, Zhejiang, China). METHODS: The high-dosage group and low-dosage group were treated with 93.50 and 23.38 mg/kg PNS respectively per day and the huperzine A group was treated with 0.038 6 mg/kg huperzine A per day, all by intragastric administration, for 8 consecutive weeks. The same volume of double distilled water was given to the control group. MAIN OUTCOME MEASURES: After drug administration, learning and memory abilities were assessed by place navigation and spatial probe tests. The recording indices consisted of escape latency (time-to-platform), and the percentage of swimming time spent in each quadrant. The number of A β 1-40, A β 1-42 and App immunopositive neurons in the brains of SAMP8 mice w