Targeted deletion of HYBID (hyaluronan binding protein involved in hyaluronan depolymerization/ KIAA1199/CEMIP) decreases dendritic spine density in the dentate gyrus through hyaluronan accumulation

摘要

HYBID (hyaluronan binding protein involved in hyaluronan [HA] depolymerization, KIAA1199/CEMIP) is a key player in HA depolymerization of the skin fibroblasts, arthritic synovial fibroblasts, and brain. Our previous study demonstrated thatHybidknock-out (KO) mice showed spatial memorial impairment, which is accompanied by the accumulation of high molecular weight HA in the hippocampus. However, the mechanism underlying cognitive impairment byHybiddeficiency remains unclear. In the present study, we examined the HA distribution patterns in the brains of wild-type (WT) andHybidKO mice by HA staining using HA binding protein, and found that inHybidKO mice, HA is accumulated and doublecortin-positive immature neurons aresignificantlydecreased in the dentate gyrus of the hippocampus, whereHybidmRNA is highly expressed in WT mice. The Golgi-Cox staining demonstrated that the dendritic spine density is significantly decreased in the dentate gyrus granule cells inHybidKO mice. These results suggest thatHybid-mediated HA degradation is critical for the synaptic formation process by contributing to cognitive functions, such as learning and memory, in the mouse brain.