Delays in GABAergic interneuron development and behavioral inhibition after prenatal stress

产前压力导致 GABA 能中间神经元发育延迟和行为抑制

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作者:Stephanie J Lussier, Hanna E Stevens

Abstract

Prenatal stress is associated with altered behavioral, cognitive, and psychiatric outcomes in offspring. Due to the importance of GABAergic systems in normal development and in psychiatric disorders, prenatal stress effects on these neurons have been investigated in animal models. Prenatal stress delays GABAergic progenitor migration, but the significance of these early developmental disruptions for the continued development of GABAergic cells in the juvenile brain is unclear. Here, we examined effects of prenatal stress on populations of GABAergic neurons in juvenile and adult medial frontal cortex (mFC) and hippocampus through stereological counting, gene expression, and relevant anxiety-like and social behaviors. Postnatally, the total GABAergic cell number that peaks in adolescence showed altered trajectories in mFC and hippocampus. Parvalbumin neuron proportion in juvenile brain was altered by prenatal stress, but parvalbumin gene expression showed no differences. In adult brain, parvalbumin neuron proportions were altered by prenatal stress with opposite gene expression changes. Adult prenatally stressed offspring showed a lack of social preference on a three-chambered task, increased anxiety-like behavior on the elevated plus maze, and reduced center time in an open field. Despite a lack of significant group differences in adult total GABAergic cell populations, performance of these tasks was correlated with GABAergic populations in mFC and hippocampus. In conclusion, prenatal stress resulted in a delay in GABAergic cell number and maturation of the parvalbumin subtype. Influences of prenatal stress on GABAergic populations during developmentally dynamic periods and during adulthood may be relevant to the anxiety-like behaviors that occur after prenatal stress. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 1078-1091, 2016.

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