This study investigated the effects of progesterone(P4) on the production and survival of neurons in the hippocampal dentate gyrus of adult male mice.The administration of P4(4 mg/kg) for 3 consecutive days beginning ...This study investigated the effects of progesterone(P4) on the production and survival of neurons in the hippocampal dentate gyrus of adult male mice.The administration of P4(4 mg/kg) for 3 consecutive days beginning on the 0-2 nd day after the first BrdU-injection(BrdU-D0-2) produced an approximately twofold increase in the number of 28-and 56-day-old BrdU(+) cells in comparison to the controls,whereas it did not alter the number of 24 /48-h-old BrdU(+) cells.P4 preferentially promoted the survival of newborn neurons when administered at BrdU-D5-7,but not at BrdU-D10-12 and BrdU-D15-17.Androstenedione(Ad),testosterone(TE),or estradiol(E2) at the same-dose of P4,when administered at BrdU-D0-2,could not replicate the effect of P4,while the inhibition of 5 alpha-reductase by finasteride did not affect the P4-action,indicating that the P4-effect is exerted by P4 itself but not by its metabolites.On the other hand,the P4R antagonist RU486 partially suppressed the P4-effect,while inhibitors for Src,MEK,or PI3K totally suppressed the P4-effect.Finally,the P4-enhanced survival of newborn neurons was accompanied by a potentiation of spatial learning and memory,which was P4R-dependent.These findings suggest that P4 enhances the survival of newborn neurons through P4R and /or the Src-ERK and PI3K pathways independent of its influence on cell proliferation,which is well correlated with the potentiated spatial cognitive function of P4-treated animals.展开更多
目的观察不同程度慢性间歇性低氧对大鼠齿状回神经细胞Nogo-A和NgR的影响及意义。方法将成年雄性Wistar大鼠45只,随机分为对照组、5%间歇低氧组、10%间歇低氧组,每组15只。又按时间分为7、14和28d 3个时间点,每个时间点5只。5%间歇低氧...目的观察不同程度慢性间歇性低氧对大鼠齿状回神经细胞Nogo-A和NgR的影响及意义。方法将成年雄性Wistar大鼠45只,随机分为对照组、5%间歇低氧组、10%间歇低氧组,每组15只。又按时间分为7、14和28d 3个时间点,每个时间点5只。5%间歇低氧组和10%间歇低氧组分别暴露于间歇性低氧条件下(暴露时间8h/d)。HE染色观察齿状回神经细胞形态变化,应用免疫组织化学法检测Nogo-A和NgR的表达水平。结果与对照组比较,5%间歇低氧组和10%间歇低氧组齿状回神经元结构受损,神经元密度明显减少(18.45±3.05,22.36±2.96 vs 28.96±4.12,P<0.05),于28d达高峰,且以5%间歇低氧组更显著(P<0.05);各时间点Nogo-A和NgR蛋白表达均增加(P<0.05),于28d达高峰,以5%间歇低氧组更显著(P<0.05)。结论不同程度慢性间歇性低氧可以引起大鼠齿状回Nogo-A和NgR表达水平增加,神经元结构受损和密度减少,可能与其抑制神经纤维修复有关。展开更多
文摘This study investigated the effects of progesterone(P4) on the production and survival of neurons in the hippocampal dentate gyrus of adult male mice.The administration of P4(4 mg/kg) for 3 consecutive days beginning on the 0-2 nd day after the first BrdU-injection(BrdU-D0-2) produced an approximately twofold increase in the number of 28-and 56-day-old BrdU(+) cells in comparison to the controls,whereas it did not alter the number of 24 /48-h-old BrdU(+) cells.P4 preferentially promoted the survival of newborn neurons when administered at BrdU-D5-7,but not at BrdU-D10-12 and BrdU-D15-17.Androstenedione(Ad),testosterone(TE),or estradiol(E2) at the same-dose of P4,when administered at BrdU-D0-2,could not replicate the effect of P4,while the inhibition of 5 alpha-reductase by finasteride did not affect the P4-action,indicating that the P4-effect is exerted by P4 itself but not by its metabolites.On the other hand,the P4R antagonist RU486 partially suppressed the P4-effect,while inhibitors for Src,MEK,or PI3K totally suppressed the P4-effect.Finally,the P4-enhanced survival of newborn neurons was accompanied by a potentiation of spatial learning and memory,which was P4R-dependent.These findings suggest that P4 enhances the survival of newborn neurons through P4R and /or the Src-ERK and PI3K pathways independent of its influence on cell proliferation,which is well correlated with the potentiated spatial cognitive function of P4-treated animals.
文摘目的探讨脑出血是否能促进大鼠海马齿状回神经再生。方法使用Western blotting、免疫组化染色和免疫荧光双标等方法并结合激光共聚焦显微镜技术对脑出血大鼠海马齿状回神经再生进行检测。结果与正常对照大鼠比较,同侧海马齿状回DCX蛋白在脑出血1 d即表达增强(0.127±0.088 vs 0.202±0.062),14 d达到高峰(0.771±0.108,P<0.01),28 d开始降低(0.582±0.121,P<0.01)。同时发现DCX和BrdU免疫阳性细胞以及DCX和BrdU免疫双标细胞出现在海马齿状回。与对照组相比,脑出血28 d大鼠海马齿状回颗粒细胞层BrdU和NeuN免疫双标细胞显著增加(1.808±1.020 vs 5.654±1.671,P<0.01)。结论脑出血能促进大鼠海马齿状回神经再生。
文摘目的观察不同程度慢性间歇性低氧对大鼠齿状回神经细胞Nogo-A和NgR的影响及意义。方法将成年雄性Wistar大鼠45只,随机分为对照组、5%间歇低氧组、10%间歇低氧组,每组15只。又按时间分为7、14和28d 3个时间点,每个时间点5只。5%间歇低氧组和10%间歇低氧组分别暴露于间歇性低氧条件下(暴露时间8h/d)。HE染色观察齿状回神经细胞形态变化,应用免疫组织化学法检测Nogo-A和NgR的表达水平。结果与对照组比较,5%间歇低氧组和10%间歇低氧组齿状回神经元结构受损,神经元密度明显减少(18.45±3.05,22.36±2.96 vs 28.96±4.12,P<0.05),于28d达高峰,且以5%间歇低氧组更显著(P<0.05);各时间点Nogo-A和NgR蛋白表达均增加(P<0.05),于28d达高峰,以5%间歇低氧组更显著(P<0.05)。结论不同程度慢性间歇性低氧可以引起大鼠齿状回Nogo-A和NgR表达水平增加,神经元结构受损和密度减少,可能与其抑制神经纤维修复有关。
