Herpes Simplex Virus Type ‐1 Infection Impairs Adult Hippocampal Neurogenesis via Amyloid‐β Protein Accumulation

Herpes simplex virus type ‐1 infection of adult hippocampal neural stem cells triggers cleavage of amyloid precursor protein with consequent intracellular accumulation of amyloid‐β protein. Following infection, neural stem cells exhibit reduced proliferation and impaired neuronal differentiation in favor of glial phenot ype with respect to mock‐infected neural stem cells. AbstractWe previously reported that Herpes simplex virus type ‐1 (HSV‐1) infection of cultured neurons triggered intracellular accumulation of amyloid‐β protein (Aβ) markedly impinging on neuronal functions. Here, we demonstrated that HSV‐1 affects in vitro and in vivo adult hippocampal neurogenesis by reducing neural stem/progenitor cell (NSC) proli feration and their neuronal differentiation via intracellular Aβ accumulation. Specifically, cultured NSCs were more permissive for HSV‐1 replication than mature neurons and, once infected, they exhibited reduced proliferation (assessed by 5′‐bromo‐deoxyuridine incorporation, Ki67 immunorea ctivity, and Sox2 mRNA expression) and impaired neuronal differentiation in favor of glial phenotype (evaluated by immunoreactivity for the neuronal marker MAP2, the glial marker glial fibrillary astrocyte protein, and the expression of the proneuronal genesMash1 andNeuroD1). Similarly, impaired adult neurogenesis was observed in the subgranular zone of hippocampal dentate gyrus of an in vivo model of recurrent HSV ‐1 infections, that we recently s...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Tissue ‐Specific Stem Cells Source Type: research