Tau knockout mitigates long-term cognitive impairment following neonatal sepsis via mechanisms involving dendritic structural remodelling and adult hippocampal neurogenesis.

One of the leading causes of morbidity and mortality in newborns and preterm infants is neonatal sepsis, which is defined as a systemic inflammatory response caused by a suspected or confirmed infection that occurs during the first month of life. Adolescents who survive neonatal sepsis often experience severe long-term cognitive impairment and unfavourable neurological outcomes. The foetal brain expresses the Tau protein, a neuronal microtubule-associated protein that is essential for modulating neuronal development, and negative neurodevelopmental effects are linked to aberrant Tau expression. In this study, we investigated the possible role of Tau in the long-term memory and cognitive function deficits caused by neonatal sepsis. We discovered that Tau silencing could attenuate the memory impairment in adolescents caused by early-life inflammation. Furthermore, Tau silencing ameliorated this loss of long-term memory and cognitive function by promoting dendritic structural remodelling in granule neurons and adult hippocampal neurogenesis (AHN) in the hippocampus dentate gyrus (DG). Together, these results suggest that Tau is a possible molecular target for treating neonatal sepsis-induced brain damage and that Tau may influence deficits in long-term memory and cognitive function caused by neonatal sepsis by interfering with the dendritic structure of granule neurons and AHN during neuronal development.