Presenter Information

Yashika S. Kamte, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA-15282

Manisha N. Chandwani, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA-15282

Dr. Lauren A. O'Donnell, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA-15282

Abstract

The neuropathological outcomes of a viral infection in the brain are often age-dependent. Infection of the immature CNS can lead to impairment of neural/stem progenitor cell (NSPCs) activity. NSPCs are multi-potent progenitor cells of the CNS and are responsible for populating the brain with neurons, astrocytes, and oligodendrocytes during development. Viral infections may alter NSPC activity via two mechanisms; directly by infection of the NSPC or indirectly due to the anti-viral immune response. Here, we examined the impact of a neurotropic infection on NSPC activity in pediatric mice (postnatal day 10), where brain and immune system development is ongoing. In order to define how anti-viral immunity affected NSPC activity, we used a mouse model of neuron restricted measles virus (MV) infection, where the virus selectively infects mature neurons and NSPCs are spared from infection. Flow cytometric analysis on the hippocampus and sub-ventricular zone (SVZ) showed a significant reduction in NSPC numbers at 9 days post infection (dpi). Mature neurons were increased in both the hippocampus and SVZ at 9 dpi, while the SVZ alone showed a decrease in immature neurons at this time point. Innate (neutrophils, macrophage/microglia, NK cells) and adaptive immune cells (T and B cells) were significantly higher in the infected group at 9 dpi. The decline in the NSPC pool showed a strong negative correlation with immune cell infiltration in the brain. Our results suggest that pediatric NSPC pool contracts in different brain regions during a CNS viral infection, which may be indicative of NSPC death, inhibition of proliferation, or increased differentiation. Current studies aim to determine the mechanism behind NSPC cell loss early in infection and to define the long-term effects of viral infection on the NSPC pool in surviving mice.

School

School of Pharmacy

Advisor

Dr. Lauren A. O'Donnell

Submission Type

Paper

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The pediatric anti-viral immune response impairs neural stem/progenitor cell activity

The neuropathological outcomes of a viral infection in the brain are often age-dependent. Infection of the immature CNS can lead to impairment of neural/stem progenitor cell (NSPCs) activity. NSPCs are multi-potent progenitor cells of the CNS and are responsible for populating the brain with neurons, astrocytes, and oligodendrocytes during development. Viral infections may alter NSPC activity via two mechanisms; directly by infection of the NSPC or indirectly due to the anti-viral immune response. Here, we examined the impact of a neurotropic infection on NSPC activity in pediatric mice (postnatal day 10), where brain and immune system development is ongoing. In order to define how anti-viral immunity affected NSPC activity, we used a mouse model of neuron restricted measles virus (MV) infection, where the virus selectively infects mature neurons and NSPCs are spared from infection. Flow cytometric analysis on the hippocampus and sub-ventricular zone (SVZ) showed a significant reduction in NSPC numbers at 9 days post infection (dpi). Mature neurons were increased in both the hippocampus and SVZ at 9 dpi, while the SVZ alone showed a decrease in immature neurons at this time point. Innate (neutrophils, macrophage/microglia, NK cells) and adaptive immune cells (T and B cells) were significantly higher in the infected group at 9 dpi. The decline in the NSPC pool showed a strong negative correlation with immune cell infiltration in the brain. Our results suggest that pediatric NSPC pool contracts in different brain regions during a CNS viral infection, which may be indicative of NSPC death, inhibition of proliferation, or increased differentiation. Current studies aim to determine the mechanism behind NSPC cell loss early in infection and to define the long-term effects of viral infection on the NSPC pool in surviving mice.