| First Author | Wang J | Year | 2020 |
| Journal | Biochem Biophys Res Commun | Volume | 525 |
| Issue | 4 | Pages | 989-996 |
| PubMed ID | 32173526 | Mgi Jnum | J:301167 |
| Mgi Id | MGI:6502931 | Doi | 10.1016/j.bbrc.2020.03.030 |
| Citation | Wang J, et al. (2020) PGC-1alpha regulate critical period plasticity via gene x environment interaction in the developmental trajectory to schizophrenia. Biochem Biophys Res Commun 525(4):989-996 |
| abstractText | Genes and environmental conditions are thought to interact in the development of postnatal brain in schizophrenia (SZ). Genome wide association studies have identified that PPARGC1A being one of the top candidate genes for SZ. We previously reported GABAergic neuron-specific PGC-1alpha knockout mice (Dlx5/6-Cre:PGC-1alpha(fl/fl)) presented some characteristic features of SZ. However, there is a fundamental gap of the molecular mechanism by which PGC-1alpha gene involved in the developmental trajectory to SZ. To explore whether PGC-1alpha regulates environmental factors interacting with genetic susceptibility to trigger symptom onset and disease progression, PGC-1alpha deficient mice were utilized to model genetic effect and an additional oxidative stress was induced by GBR injection. We confirm that PGC-1alpha gene deletion prolongs critical period (CP) timing, as revealed by delaying maturation of PV interneurons (PVIs), including their perineuronal nets (PNNs). Further, we confirm that gene x environment (G x E) influences CP plasticity synergistically and the interaction varies as a function of age, with the most sensitive period being at preweaning stage, and the least sensitive one at early adult age in PGC-1alpha deficient mice. Along this line, we find that the synergic action of G x E is available in ChABC-infusion PGC-1alpha KO mice, even though during the adulthood, and the neuroplasticity seems to remain open to fluctuate. Altogether, these results refine the observations made in the PGC-1alpha deficient mice, a potential mouse model of SZ, and illustrate how PGC-1alpha regulates CP plasticity via G x E interaction in the developmental trajectory to SZ. |
