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

M. Jafari, V. Haist, W. Baumgartner, S. Wagner, V. M. Stein, A. Tipold, H. Wendt and H. Potschka (2012) Neuropathology and Applied Neurobiology 38, 647–664 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.