| Literature DB >> 31138511 |
Min Hee Park1, Byung Jo Choi2, Min Seock Jeong2, Ju Youn Lee1, In Kyung Jung1, Kang Ho Park1, Hye Won Lee3, Tomoyuki Yamaguchi4, Hugo H Marti5, Beom Hee Lee6, Edward H Schuchman7, Hee Kyung Jin8, Jae-Sung Bae9.
Abstract
Gliosis in Niemann-Pick type C (NP-C) disease is characterized by marked changes in microglia and astrocytes. However, the gliosis onset and progression in NP-C has not been systematically studied, nor has the mechanism underlying this finding. Here, we found early gliosis in the subventricular zone (SVZ) of NP-C mice. Neural progenitor damage by Npc1 mutation suppressed vascular endothelial growth factor (VEGF) expression and further induced microglia activation followed by astrogliosis. Interestingly, excessive astrogliosis in the SVZ induced neural progenitor retention and/or migration into thalamus via astrocyte-derived VEGF, resulting in acceleration of thalamic and cortical gliosis through thalamo-cortical pathways. Transplantation of VEGF-overexpressing neural stem cells into the SVZ improved whole-brain pathology of NP-C mice. Overall, our data provide a new pathological perspective on NP-C neural pathology, revealing abnormalities in the subventricular-thalamo-cortical circuit of NP-C mouse brain and highlighting the importance of the SVZ microenvironment as a therapeutic target for NP-C disease.Entities:
Keywords: Niemann-Pick type C disease; gliosis; neural progenitor retention and/or migration; subventricular zone; thalamo-cortical pathway; vascular endothelial growth factor
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Year: 2019 PMID： 31138511 PMCID： PMC6697385 DOI： 10.1016/j.ymthe.2019.05.008
Source DB: PubMed Journal: Mol Ther ISSN： 1525-0016 Impact factor: 11.454