齿状回
帕尔瓦布明
海马结构
后代
海马体
神经科学
免疫系统
溴脱氧尿苷
内分泌学
加巴能
内科学
神经发生
生物
抑制性突触后电位
医学
免疫学
免疫组织化学
怀孕
遗传学
作者
Zhi Zhang,Henriette van Praag
标识
DOI:10.1016/j.bbi.2014.10.010
摘要
Schizophrenia is associated with deficits in the hippocampus, a brain area important for learning and memory. The dentate gyrus (DG) of the hippocampus develops both before and after birth. To study the relative contribution of mature and adult-born DG granule cells to disease etiology, we compared both cell populations in a mouse model of psychiatric illness resulting from maternal immune activation. Polyriboinosinic–polyribocytidilic acid (PolyIC, 5 mg/kg) or saline was given on gestation day 15 to pregnant female C57Bl/6 mice. Male offspring (n = 105), was administered systemic bromodeoxyuridine (BrdU, 50 mg/kg) (n = 52) or intracerebral retroviral injection into the DG (n = 53), to label dividing cells at one month of age. Two months later behavioral tests were performed to evaluate disease phenotype. Immunohistochemistry and whole-cell patch clamping were used to assess morphological and physiological characteristics of DG cells. Three-month-old PolyIC exposed male offspring exhibited deficient pre-pulse inhibition, spatial maze performance and motor coordination, as well as increased depression-like behavior. Histological analysis showed reduced DG volume and parvalbumin positive interneuron number. Both mature and new hippocampal neurons showed modifications in intrinsic properties such as increased input resistance and lower current threshold, and decreased action potential number. Reduced GABAergic inhibitory transmission was observed only in mature DG neurons. Differential impairments in mature DG cells and adult-born new neurons may have implications for behavioral deficits associated with maternal immune activation.
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