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

Biochem. Biophys. Res. Commun.2018 Sep 10;503(3):1934-1940. Epub 2018 Jul 27
Yuta Yoshino 1 , Masamitsu Shimazawa 1 , Shinsuke Nakamura 1 , Shintaro Inoue 2 , Hiroyuki Yoshida 3 , Masayuki Shimoda 4 , Yasunori Okada 5 , Hideaki Hara 6
Yuta Yoshino 1 , Masamitsu Shimazawa 1 , Shinsuke Nakamura 1 , Shintaro Inoue 2 , Hiroyuki Yoshida 3 , Masayuki Shimoda 4 , Yasunori Okada 5 , Hideaki Hara 6
+ et al

[No authors listed]

Author information
  • 1 Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
  • 2 Cosmetic Health Science, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
  • 3 Biological Science Research, Kao Corporation, 5-3-28 Kotobuki-cho, Odawara 250-0002, Japan.
  • 4 Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-0016, Japan.
  • 5 Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-0016, Japan; Department of Pathophysiology for Locomotive and Neoplastic Diseases, Juntendo University Graduate School of Medicine, Tokyo, Japan.
  • 6 Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan. Electronic address: hidehara@gifu-pu.ac.jp.

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 that Hybid knock-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 by Hybid deficiency remains unclear. In the present study, we examined the HA distribution patterns in the brains of wild-type (WT) and Hybid KO mice by HA staining using HA binding protein, and found that in Hybid KO mice, HA is accumulated and doublecortin-positive immature neurons are significantly decreased in the dentate gyrus of the hippocampus, where Hybid mRNA 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 in Hybid KO mice. These results suggest that Hybid-mediated HA degradation is critical for the synaptic formation process by contributing to cognitive functions, such as learning and memory, in the mouse brain.

KEYWORDS: Dendritic spine, Dentate gyrus, HYBID, Hippocampus, Hyaluronan, Neurogenesis

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