| First Author | Yu D | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 18 | Pages | eabm2545 |
| PubMed ID | 35544642 | Mgi Jnum | J:324465 |
| Mgi Id | MGI:7278219 | Doi | 10.1126/sciadv.abm2545 |
| Citation | Yu D, et al. (2022) Microglial GPR56 is the molecular target of maternal immune activation-induced parvalbumin-positive interneuron deficits. Sci Adv 8(18):eabm2545 |
| abstractText | Parvalbumin-positive (PV(+)) interneurons play a critical role in maintaining circuit rhythm in the brain, and their reduction is implicated in autism spectrum disorders. Animal studies demonstrate that maternal immune activation (MIA) leads to reduced PV(+) interneurons in the somatosensory cortex and autism-like behaviors. However, the underlying molecular mechanisms remain largely unknown. Here, we show that MIA down-regulates microglial Gpr56 expression in fetal brains in an interleukin-17a-dependent manner and that conditional deletion of microglial Gpr56 [Gpr56 conditional knockout (cKO)] mimics MIA-induced PV(+) interneuron defects and autism-like behaviors in offspring. We further demonstrate that elevated microglial tumor necrosis factor-alpha expression is the underlying mechanism by which MIA and Gpr56 cKO impair interneuron generation. Genetically restoring Gpr56 expression in microglia ameliorates PV(+) interneuron deficits and autism-like behaviors in MIA offspring. Together, our study demonstrates that microglial GPR56 plays an important role in PV(+) interneuron development and serves as a salient target of MIA-induced neurodevelopmental disorders. |
