Three cell-based models shed light on how herpes simplex virus type 1 (HSV-1) infection, which can spread to the fetal brain during pregnancy, may contribute to various neurodevelopmental disabilities and long-term neurological problems into adulthood, say researchers.
According to the study, published in the journal PLOS Pathogens, HSV-1 is a highly prevalent pathogen that can cause lifelong neurological problems such as cognitive dysfunction, learning disabilities, and dementia.

To address this gap in knowledge, the researchers generated three different cell-based neurodevelopmental disorder models, including a 2D layer of cells and a 3D brain-like structure.

These models are based on human induced pluripotent stem cells (hiPSCs) - immature, embryonic stem cell-like cells that are generated by genetically reprogramming specialized adult cells.
According to the researchers, HSV-1 infection in neural stem cells derived from hiPSCs resulted in activation of the caspase-3 apoptotic pathway, which initiates programmed cell death.
HSV-1 infection also impaired the production of new neurons, and hindered the ability of hiPSC-derived neural stem cells to convert into mature neurons through a process called neuronal differentiation.

In addition, the 3D model showed that HSV-1 infection promotes the abnormal proliferation and activation of non-neuronal cells called microglia, accompanied by the activation of inflammatory molecules, such as TNF-a, IL-6, IL-10, and IL-4.
According to the authors, the findings open new therapeutic avenues for targeting viral reservoirs relevant to neurodevelopmental disorders.
"This study provides novel evidence that HSV-1 infection impaired human brain development and contributed to the neurodevelopmental disorder pathogen hypothesis," authors wrote.

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