Neurochemical characterization of embryonic brain development in trisomy 19 (Ts19) mice: implications of selective deficits observed for abnormal neural development in aneuploidy.

Neurochemical characterization of embryonic brain development in trisomy 19 (Ts19) mice: implications of selective deficits observed for abnormal neural development in aneuploidy.
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19 三体 (Ts19) 小鼠胚胎脑发育的神经化学特征:观察到的选择性缺陷对非整倍体神经发育异常的影响。

DOI:
10.1002/dvg.1020080409
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发表时间:
1987
期刊:
Developmental genetics
影响因子:
--
通讯作者:
Coyle,JT
Coyle,JT
中科院分区:
--
文献类型:
--
作者:
Saltarelli,MD;Forloni,GL;Oster-Granite,ML;Gearhart,JD;Coyle,JT

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在这项研究中,我们研究了选定的大脑区域(大脑半球,间脑/脑干)在胎儿(妊娠第14至18天)19三体(Ts 19)小鼠的神经化学谱。我们在Ts 19小鼠中观察到的神经化学特征与我们先前在Ts 16小鼠中观察到的特征有很大不同。胆碱乙酰转移酶(ChAT)的活性显着降低大脑半球,但不是在脑干/间脑,胎儿Ts 19小鼠大脑,表明端脑胆碱能神经元的选择性脆弱性。此外,谷氨酸脱羧酶(GAD)的活性显着降低,在两个半球和间脑/脑干的晚孕Ts 19胎儿,表明选择性的GABA能神经元的脆弱性,以及。虽然儿茶酚胺能和多巴胺能标记物的水平显着降低,在孕龄后期,多巴胺(DA)的相对周转率,测量的DOPAC/DA的比例,在Ts 19小鼠显着升高。无论是减少大脑皮层的各种细胞区的厚度,也没有减少大脑皮层的细胞密度占Ts 19小鼠中观察到的神经化学参数的变化。这些结果表明,三倍的特定基因对各自的染色体的影响,而不是一个普遍的破坏发展的动态平衡所造成的额外的染色体材料,可能会产生选择性的改变,在这两个小鼠三体中观察到的神经化学和神经解剖标志物。
In this study, we examined the neurochemical profiles of selected brain regions (cerebral hemispheres, diencephalon/brainstem) in fetal (day 14 to 18 gestation) trisomy 19 (Ts19) mice. The neurochemical characteristics we observed in Ts19 mice were quite different from those we observed previously in Ts16 mice. Choline acetyltransferase (ChAT) activity was reduced significantly in the cerebral hemispheres, but not in the brainstem/diencephalon, of the fetal Ts19 mouse brain, suggesting a selective vulnerability of telencephalic cholinergic neurons. Additionally, the activity of glutamic acid decarboxylase (GAD) was reduced significantly in both hemispheres and diencephalon/brainstem of late gestation Ts19 fetuses, suggesting a selective vulnerability of GABAergic neurons as well. While the levels of catecholaminergic and dopaminergic markers were reduced significantly at late gestational ages, the relative rate of turnover of dopamine (DA), measured by the ratio of DOPAC/DA, was elevated significantly in Ts19 mice. Neither reduction in the thickness of various cellular zones of the cerebral cortex nor reduced cell density of the cerebral cortex accounts for the alterations in neurochemical parameters observed in Ts19 mice. These results suggest that the effects of the triplication of specific genes on the respective chromosomes, rather than a generalized disruption of developmental homeostasis resulting from extra chromosomal material, may produce selective alterations in neurochemical and neuroanatomical markers observed in these two mouse trisomies.