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ADAMTS18 Deficiency Affects Neuronal Morphogenesis and Reduces the Levels of Depression-like Behaviors in Mice.

Rui Zhu | Yi-Hsuan Pan | Lijie Sun | Tianhao Zhang | Caiyun Wang | Shuai Ye | Ning Yang | Tiantian Lu | Thomas Wisniewski | Suying Dang | Wei Zhang
Neuroscience | 2019

The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that modify extracellular matrix components and play crucial roles in development and numerous diseases. ADAMTS18 is a member of the ADAMTS family, and genome-wide association studies made an initial association of ADAMTS18 with white matter integrity in healthy people of 72-74 years old. However, the potential roles of ADAMTS18 in central nervous system remain unclear. In this study, we showed that Adamts18 mRNA is highly abundant in developing brains, especially in the cerebellum granular cell layer and the hippocampus dentate gyrus (DG) granular cell layer. Adamts18 knockout (KO) mice displayed higher dendritic branching complexity and spine density on hippocampal DG granular cells. Behavioral tests showed that Adamts18 KO mice had reduced levels of depression-like behaviors compared to their wild-type (WT) littermates. The increased neurite formation could be attributed in part to reduced phosphorylation levels of the collapsin response mediator protein-2 (CRMP2) due to activation of the laminin/PI3K/AKT/GSK-3β signaling pathway. Our findings revealed a critical role of ADAMTS18 in neuronal morphogenesis and emotional control in mice.

Pubmed ID: 30579834

Research resources used in this publication

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Associated grants

  • Agency: NIA NIH HHS, United States
    Id: P01 AG060882
  • Agency: NIA NIH HHS, United States
    Id: P30 AG066512
  • Agency: NIA NIH HHS, United States
    Id: RF1 AG058267

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