Effects and mechanisms of glycemic variability on apoptosis in mouse hippocampal neuronal HT-22 cells

• Glycemic variability and sustained high glucose both induce apoptosis in mouse hippocampal HT-22 cells, with sustained high glucose showing a stronger effect. • Glycemic variability upregulates HDAC4 and downregulates SIRT1 expression, leading to histone acetylation imbalance. • The HDAC4/SIRT1 axis modulates the expression of pro-apoptotic (Bax, Caspase-3) and anti-apoptotic (Bcl-2) genes via epigenetic mechanisms. • Glycemic variability increases oxidative stress (ROS) and histone deacetylase activity, contributing to neuronal damage.