Viral Investigation of Regulatory Human Astrocytes to Understand the Glymphatic System

Abstract

Alzheimer's disease (AD), and other neurodegenerative diseases, results from an extracellular accumulation of beta-amyloid plaques, which are composed of misfolded peptide oligomers of beta-amyloid. The accumulation is thought to be due to the failure of the glymphatic system, a waste clearance system in brain, which uses aquaporin-4 (AQP4) protein water channels. This protein exists as heterotetramers of M1 and M23 isoforms from splice variants of AQP4. Previous studies suggested that Herpes Simplex Virus-1 (HSV-1) infection of the central nervous system (CNS) may be correlated to AD development. However, the effect of HSV-1 on the glymphatic system has not been definitively established. The objective of this study was to investigate HSV-1 infection on AQP4 expression in human brain-derived glial cells. Our preliminary results suggest that HSV-1 infection of the cells leads to lower protein levels of M23 isoform. These results suggest that HSV-1 infection may potentially interfere with the function of the glymphatic system through the reduction of the AQP4 protein.