Early ciliary and prominin-1 dysfunctions precede neurogenesis impairment in a mouse model of type 2 diabetes

NEUROBIOLOGY OF DISEASE

卷:108

Article

Bachor, Tomas P.¹  Karbanova, Jana^2,3  Buttner, Edgar^2,3  Bermudez, Vicente^1,2,3  Marquioni-Ramella, Melisa¹  Carmeliet, Peter^4,5  Corbeil, Denis^2,3  Suburo, Angela M.¹ 

[1] Univ Austral, CONICET, IIMT, B1629AHJ, Pilar, Argentina

[2] Tech Univ Dresden, Tissue Engn Labs, Biotechnol Ctr BIOTEC, D-01307 Dresden, Germany

[3] Tech Univ Dresden, Tissue Engn Labs, DFG Ctr Regenerat Therapies Dresden CRTD, D-01307 Dresden, Germany

[4] VIB, Ctr Canc Biol, Lab Angiogenesis & Vasc Metab, Leuven, Belgium

[5] Katholieke Univ Leuven, Dept Oncol, Lab Angiogenesis & Vasc Metab, Leuven, Belgium

关键词: CD133;    Cilia;    Diabetes;    Glucose transporter;    Neurogenesis;    Prominin, Subventricular zone;    Neurodegeneration;    Streptozotocin;    Nicotinamide;   

DOI  :  10.1016/j.nbd.2017.07.010

来源: Elsevier

【 摘 要 】

Diabetes mellitus (DM) is reaching epidemic conditions worldwide and increases the risk for cognition impairment and dementia. Here, we postulated that progenitors in adult neurogenic niches might be particularly vulnerable. Therefore, we evaluated the different components of the mouse subventricular zone (SVZ) during the first week after chemical induction of type 1 and type 2 diabetes-like (T1DM and T2DM) conditions. Surprisingly, only T2DM mice showed SVZ damage. The initial lesions were localized to ependymal cilia, which appeared disorientated and clumped together. In addition, they showed delocalization of the ciliary membrane protein prominin-1. Impairment of neuroprogenitor proliferation, neurogenic marker abnormalities and ectopic migration of neuroblasts were found at a later stage. To our knowledge, our data describe for the first time such an early impact of T2DM on the SVZ. This is consistent with clinical data indicating that brain damage in T2DM patients differs from that in T1DM patients. (C) 2017 Elsevier Inc. All rights reserved.

【 授权许可】

Free