Impact of Theiler's virus infection on hippocampal neuronal progenitor cells: differential effects in two mouse strains

Impact of Theiler's virus infection on hippocampal neuronal progenitor cells: differential effects in two mouse strains
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DOI:
10.1111/j.1365-2990.2012.01256.x
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发表时间:
2012-12-01
影响因子:
5
通讯作者:
Potschka, H.
Potschka, H.
中科院分区:
医学2区
文献类型:
--
作者:
Jafari, M.;Haist, V.;Potschka, H.

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M. Jafari,V. Haist,W. Baumgartner,S.瓦格纳斯泰因A. Tipold,H. Wendt和H. Potschka(2012)Neuropathology and Applied Neurobiology 38,647664 Impact of Theiler's virus infection on hippocampal neuronal progenitor cells:differential effects in two mouse strains目的:讨论海马神经发生中的疾病相关改变是导致中枢神经系统疾病长期后果的重要因素。因此,本研究旨在确定Theiler小鼠脑脊髓炎病毒感染对海马细胞增殖、神经元祖细胞和神经发生的影响,以及小胶质细胞对各自疾病相关改变的影响。研究方法:在病程不同的两种小鼠品系中评价了感染的影响,在C57 BL/6小鼠中为急性脊髓灰质炎,随后为病毒消除,在SJL/J小鼠中为慢性脱髓鞘疾病。结果:无论小鼠品系如何,用低神经毒力BeAn株感染均未产生显著的急性效应。在慢性期,神经元祖细胞和早期有丝分裂后神经元的数量显着减少感染的SJL/J小鼠,而没有长期的改变,观察到C57 BL/6小鼠。在两种小鼠品系中观察到小胶质细胞活化的对比过程,SJL/J小鼠中活化的小胶质细胞数量早期增加,C57 BL/6小鼠中延迟增加。定量分析没有证实激活的小胶质细胞的数量和神经元祖细胞和早期有丝分裂后神经元的数量之间的相关性。然而,流式细胞仪分析显示,小胶质细胞的功能状态的改变,这可能会影响神经元祖细胞的产生。结论:Theiler的小鼠脑脊髓炎病毒感染可以对海马神经元祖细胞群体产生延迟效应,感染后3个月出现明显的长期改变。这些改变被证明取决于菌株的易感性,并可能导致病毒性脑炎的有害后果,如认知障碍。
M. Jafari, V. Haist, W. Baumgartner, S. Wagner, V. M. Stein, A. Tipold, H. Wendt and H. Potschka (2012) Neuropathology and Applied Neurobiology 38, 647664 Impact of Theiler's virus infection on hippocampal neuronal progenitor cells: differential effects in two mouse strains Aims: Disease-associated alterations in hippocampal neurogenesis are discussed as an important factor contributing to long-term consequences of central nervous system diseases. Therefore, the study aimed to determine the impact of Theiler's murine encephalomyelitis virus infection on hippocampal cell proliferation, neuronal progenitor cells and neurogenesis as well as the influence of microglia on respective disease-associated alterations. Methods: The impact of the infection was evaluated in two mouse strains which differ in the disease course, with an acute polioencephalitis followed by virus elimination in C57BL/6 mice and a chronic demyelinating disease in SJL/J mice. Results: Infection with the low neurovirulent BeAn strain did not exert significant acute effects regardless of the mouse strain. In the chronic phase, the number of neuronal progenitor cells and early postmitotic neurones was significantly reduced in infected SJL/J mice, whereas no long-term alterations were observed in C57BL/6 mice. A contrasting course of microglia activation was observed in the two mouse strains, with an early increase in the number of activated microglia cells in SJL/J mice and a delayed increase in C57BL/6 mice. Quantitative analysis did not confirm a correlation between the number of activated microglia and the number of neuronal progenitor cells and early postmitotic neurones. However, flow cytometric analyses revealed alterations in the functional state of microglial cells which might have affected the generation of neuronal progenitor cells. Conclusions: Theiler's murine encephalomyelitis virus infection can exert delayed effects on the hippocampal neuronal progenitor population with long-term alterations evident 3 months following infection. These alterations proved to depend on strain susceptibility and might contribute to detrimental consequences of virus encephalitis such as cognitive impairment.