PGC-1α regulate critical period plasticity via gene × environment interaction in the developmental trajectory to schizophrenia.
Biochem Biophys Res Commun
; 525(4): 989-996, 2020 05 14.
Article
em En
| MEDLINE
| ID: mdl-32173526
ABSTRACT
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-1α knockout mice (Dlx5/6-CrePGC-1αfl/fl) presented some characteristic features of SZ. However, there is a fundamental gap of the molecular mechanism by which PGC-1α gene involved in the developmental trajectory to SZ. To explore whether PGC-1α regulates environmental factors interacting with genetic susceptibility to trigger symptom onset and disease progression, PGC-1α deficient mice were utilized to model genetic effect and an additional oxidative stress was induced by GBR injection. We confirm that PGC-1α 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 × environment (G × 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-1α deficient mice. Along this line, we find that the synergic action of G × E is available in ChABC-infusion PGC-1α 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-1α deficient mice, a potential mouse model of SZ, and illustrate how PGC-1α regulates CP plasticity via G × E interaction in the developmental trajectory to SZ.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Parvalbuminas
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Esquizofrenia
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Neurônios GABAérgicos
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Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo
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Interneurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article