Researchers say, three cell-based models shed light on how herpes simplex virus type 1 (HSV-1) infection, which may spread to the fetal brain during pregnancy and may also contribute to varied neurodevelopment disabilities and long-term neurological problems into adulthood.
According to the study, published in the journal PLOS Pathogens, HSV-1 is a highly common pathogen that can cause lifelong neurological problems such as cognitive dysfunction, learning disabilities, and dementia.
Study authors from Wuhan University in China said, “But progress in understanding the role of HSV-1 in human fetal brain development has been hampered by restricted access to fetal human brain tissue that also as limitations of existing animal models.”
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The researchers generated three different cell-based neurodevelopmental disorder models, including a 2D layer of cells and a 3D brain-like structure to deal with this gap in knowledge.
The models are based on the human induced pluripotent stem cells (hiPSCs) – immature embryonic stem cell-like cells that are generated by genetically reprogramming specialized adult cells.
HSV-1 infection in neural stem cells that’s derived from hiPSCs and is resulted in activation of the caspase-3 apoptotic pathway, which initiates programmed necrobiosis , consistent with the researchers.
This infection is additionally impaired the assembly of latest neurons, and has hindered the power of hiPSC-derived neural stem cells to convert into mature neurons through a process called neuronal differentiation.
Moreover, the HSV-1-infected brain imitated the pathological features of neurodevelopmental disorders within the human fetal brain, including impaired neuronal differentiation and abnormalities in brain structure.
Including that, the 3D model showed that HSV-1 infection promotes the abnormal proliferation and activation of non-neuronal cells called microglia, amid the activation of inflammatory molecules, like TNF-a, IL-6, IL-10, and IL-4.
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The authors say, the findings have 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.