| First Author | Ago Y | Year | 2023 |
| Journal | Exp Neurol | Volume | 362 |
| Pages | 114339 | PubMed ID | 36717013 |
| Mgi Jnum | J:340122 | Mgi Id | MGI:7433973 |
| Doi | 10.1016/j.expneurol.2023.114339 | Citation | Ago Y, et al. (2023) Overexpression of VIPR2 in mice results in microencephaly with paradoxical increased white matter volume. Exp Neurol 362:114339 |
| abstractText | Large scale studies in populations of European and Han Chinese ancestry found a series of rare gain-of-function microduplications in VIPR2, encoding VPAC2, a receptor that binds vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide with high affinity, that were associated with an up to 13-fold increased risk for schizophrenia. To address how VPAC2 receptor overactivity might affect brain development, we used a well-characterized Nestin-Cre mouse strain and a knock-in approach to overexpress human VPAC2 in the central nervous system. Mice that overexpressed VPAC2 were found to exhibit a significant reduction in brain weight. Magnetic resonance imaging analysis confirmed a decrease in brain size, a specific reduction in the hippocampus grey matter volume and a paradoxical increase in whole-brain white matter volume. Sex-specific changes in behavior such as impaired prepulse inhibition and contextual fear memory were observed in VPAC2 overexpressing mice. The data indicate that the VPAC2 receptor may play a critical role in brain morphogenesis and suggest that overactive VPAC2 signaling during development plays a mechanistic role in some forms of schizophrenia. |
