| First Author | Maset A | Year | 2021 |
| Journal | Proc Natl Acad Sci U S A | Volume | 118 |
| Issue | 2 | PubMed ID | 33376209 |
| Mgi Jnum | J:299609 | Mgi Id | MGI:6501278 |
| Doi | 10.1073/pnas.2016034118 | Citation | Maset A, et al. (2021) Altered Cl(-) homeostasis hinders forebrain GABAergic interneuron migration in a mouse model of intellectual disability. Proc Natl Acad Sci U S A 118(2):e2016034118 |
| abstractText | Impairments of inhibitory circuits are at the basis of most, if not all, cognitive deficits. The impact of OPHN1, a gene associate with intellectual disability (ID), on inhibitory neurons remains elusive. We addressed this issue by analyzing the postnatal migration of inhibitory interneurons derived from the subventricular zone in a validated mouse model of ID (OPHN1(-/y) mice). We found that the speed and directionality of migrating neuroblasts were deeply perturbed in OPHN1(-/y) mice. The significant reduction in speed was due to altered chloride (Cl(-)) homeostasis, while the overactivation of the OPHN1 downstream signaling pathway, RhoA kinase (ROCK), caused abnormalities in the directionality of the neuroblast progression in mutants. Blocking the cation-Cl(-) cotransporter KCC2 almost completely rescued the migration speed while proper directionality was restored upon ROCK inhibition. Our data unveil a strong impact of OPHN1 on GABAergic inhibitory interneurons and identify putative targets for successful therapeutic approaches. |
