Glucose Starvation Causes p tau S409 Increase in N2a Cells Through ATF3/PKAc α Signaling Pathway

In this work, we report that glucose starvation (GS) causes p tau S409 increase, which may participate in GS-induced neurites retraction in neuro-2a (N2a) cells. Upon GS treatment, PKAc α was stimulated at mRNA and protein levels. Luciferase reporter gene assays indicated that GS regulated PKAcα expression through a core promoter (−345 to −95 bp upstream the transcription starting site) consisting of a cis-acting element of Activating Transcription Factor 3 (ATF3). Knockdown and over-expression experiments demonstrate that ATF3 transcriptionally regulated PKAcα expression. Moreover, GS stimulated ATF3 expression in a time-dependent manner. These findings reveal that glucose starvation induces p tau S409 increase in N2a cells through an ATF3- PKAc α axis, which shed some light on the relationship between brain glucose metabolism and neurodegenerative diseases.