运动上调蛋白酶体活性促进SVZ区神经发生

Physical Running Promotes Neurogenesis of SVZ Through Enhancing Proteasome Activity

目的:观察运动后小鼠脑室室管膜下区(subventricular zone,SVZ)蛋白酶体活性变化,探讨运动促进神经发生的机制。方法:应用荧光分光光度法检测新生小鼠(Postnantal day 0,P0)、成年小鼠(Postnantal day 90,P90)及老年小鼠(Postnantal day 540,P540)SVZ蛋白酶体活性。成年小鼠自主跑轮运动4周后检测蛋白酶体活性,通过Ki67、DCX免疫荧光染色检测SVZ神经发生水平;小鼠注射MG132,观察抑制蛋白酶体活性是否影响运动对神经发生的促进作用。结果:随年龄增长,P90、P540小鼠SVZ蛋白酶体活性较P0小鼠分别下降50.9%(P<0.01)、70.4%(P<0.01)。运动后小鼠SVZ蛋白酶体活性较安静组增加39.8%(P<0.01),蛋白酶体亚单位PSMB1、PSMB2、PSMB5及PSMA3的表达水平也较安静组分别增加9.1%(P<0.05)、21.7%(P<0.01)、25.4%(P<0.01)和10.1%(P<0.05),神经发生相关指标Ki67^+、DCX^+细胞数量较安静组分别增加32.4%(P<0.01)和78.3%(P<0.001)。小鼠侧脑室注射MG132后再进行跑轮运动,MG132-运动组SVZ区Ki67^+、DCX^+细胞数量较DMSO-运动组分别下降27.6%(P<0.001)和51.5%(P<0.001)。结论:随年龄增长,蛋白酶体活性下降。运动可能通过提高SVZ蛋白酶体活性促进神经发生。

Objective To obsene the proteasome activity of physical running mice to clarify the mechanism of its pmnloting the nrurogenesis of the subventricular zone(SVZ). Methods SVZ tissues of newborn inie( Postnatal day 0, P0), adult mice (Postnatal day 90, P90) and aged niice( Postnatal day 540, P540) were isolated to detect the proteasome activity using the fluoresce nee spectrophotometry. The P90 mice were selected to establish a voluntary running wheel model, and the change of SVZ proteasome activity was observed cifter running exercises for 4 weeks, then Ki67 and DCX immunofluorescene staining was used to observe the SVZ neurogenesis of adult mice. Phe proteasome inhibitor MG132 was injected into SVZ to observe the neurogenesis level of phvsical running mice. Results The proteasome activity of SVZ decreased gradually with age, and that of P90 and P540 mice decreased 50.9%(P<0.0l ) and 70.4%(P<0.01 ) respectively compared with P0 mice. After running for 4 weeks, the proteasome activity of SVZ in P90 mice increased 39.8% compared with those sedentary nlice (P< 0.01 ), and the expression of the subunit of proteasome including PSMB1 , PSMB2, PSMB5 and PSMA3 of the running mice increased 9.1 %(P<0.05), 21.7%(P<0.01), 25.4%(P<0.01) and 10.1%(P< 0.05) compared to those sedentary ones. The number of the marker of neurogenesis including Ki67 and DCX increased 32.4%(P<0.01 ) and 78.3%(P<0.001) respectively compared to the sedenttuy mice.After injecting MG132, the number of Ki67 and DCX of the running mice decreased 27.6%(P<0.001) and 51.5%(P<0.001 ). Conclusion The proteasome activity of SVZ decreased with age. Physical running may promote neurogenesis by increasing the proteasome avtivity of SVZ.