Effects of Arcadlin on dendritic spine morphology of hippocampal granule cells in a mouse model of ischemic stroke.

Abstract

Changes in synaptic structure play critical roles in both the development and recovery processes following ischemic stroke. Previous studies have revealed that ischemic stroke strongly induces Arcadlin (Acad; also known as Paraxial protocadherin or Protocadherin-8) expression in the hippocampal dentate gyrus (DG). Although Acad has been reported to negatively regulate dendritic spine density, its detailed roles after ischemic stroke remain unclear. In this study, we found that middle cerebral artery occlusion (MCAO) localized Acad to synaptic components in the hippocampus and upregulated the short variant of Acad, which is associated with reduced dendritic spine density. MCAO significantly decreased dendritic spine density in DG granule cells. While Acad knockout did not prevent the MCAO-induced reduction in dendritic spine density, MCAO increased the proportion of exceptionally enlarged dendritic spines in DG granule cells only in Acad knockout mice. Furthermore, Acad knockout exacerbated MCAO-induced abnormal hyperlocomotion. Our findings suggest that ischemia-induced Acad in the DG exerts protective effects against ischemic stroke through the regulation of dendritic spine size, potentially limiting synaptic input to DG granule cells.