| First Author | Ren X | Year | 2021 |
| Journal | Neurobiol Dis | Volume | 154 |
| Pages | 105339 | PubMed ID | 33775822 |
| Mgi Jnum | J:306140 | Mgi Id | MGI:6706878 |
| Doi | 10.1016/j.nbd.2021.105339 | Citation | Ren X, et al. (2021) Linking cortical astrocytic neogenin deficiency to the development of Moyamoya disease-like vasculopathy. Neurobiol Dis 154:105339 |
| abstractText | Moyamoya-like vasculopathy, the "puff of smoke"-like small vessels in the brain, is initially identified in patients with Moyamoya disease (MMD), a rare cerebrovascular disease, and later found in patients with various types of neurological conditions, including Down syndrome, Stroke, and vascular dementia. It is thus of interest to understand how this vasculopathy is developed. Here, we provided evidence for cortical astrocytic neogenin (NEO1) deficiency to be a risk factor for its development. NEO1, a member of deleted in colorectal cancer (DCC) family netrin receptors, was reduced in brain samples of patients with MMD. Astrocytic Neo1-loss resulted in an increase of small blood vessels (BVs) selectively in the cortex. These BVs were dysfunctional, with leaky blood-brain barrier (BBB), thin arteries, and accelerated hyperplasia in veins and capillaries, resembled to the features of moyamoya-like vasculopathy. Additionally, we found that both MMD patient and Neo1 mutant mice exhibited altered gene expression in their cortex in proteins critical for not only angiogenesis [e.g., an increase in vascular endothelial growth factor (VEGFa)], but also axon guidance (e.g., netrin family proteins) and inflammation. In aggregates, these results suggest a critical role of astrocytic NEO1-loss in the development of Moyamoya-like vasculopathy, providing a mouse model for investigating mechanisms of Moyamoya-like vasculopathy. |
