Effects of ethanol exposure in utero on Cajal-Retzius cells in the developing cortex.

Effects of ethanol exposure in utero on Cajal-Retzius cells in the developing cortex.
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子宫内乙醇暴露对发育皮质中的 Cajal-Retzius 细胞的影响。

DOI:
10.1111/acer.12696
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发表时间:
2015
期刊:
Alcoholism, clinical and experimental research
影响因子:
--
通讯作者:
Yeh,HermesH
Yeh,HermesH
中科院分区:
--
文献类型:
--
作者:
Skorput,AlexanderGJ;Yeh,HermesH

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BackgroundPrenatal exposure to ethanol exerts teratogenic effects on the developing brain. Here, we tested the hypothesis that exposure to ethanol in utero alters the disposition of Cajal–Retzius cells that play a key role in orchestrating proliferation, migration, and laminar integration of cortical neurons in the embryonic cortex.MethodsPregnant Ebf2‐EGFP mice, harboring EGFP‐fluorescent Cajal–Retzius cells, were subjected to a 2% w/w ethanol consumption regimen starting at neural tube closure and lasting throughout gestation. Genesis of Cajal–Retzius cells was assessed by means of 5‐bromo‐2‐deoxyuridine (BrdU) immunofluorescence at embryonic day 12.5, their counts and distribution were determined between postnatal day (P)0 and P4, patch clamp electrophysiology was performed between P2 and P3 to analyze GABA‐mediated synaptic activity, and open‐field behavioral testing was conducted in P45‐P50 adolescents.ResultsIn Ebf2‐EGFP embryos exposed to ethanol in utero, we found increased BrdU labeling and expanded distribution of Cajal–Retzius cells in the cortical hem, pointing to increased genesis and proliferation. Postnatally, we found an increase in Cajal–Retzius cell number in cortical layer I. In addition, they displayed altered patterning of spontaneous GABA‐mediated synaptic barrages and enhanced GABA‐mediated synaptic activity, suggesting enhanced GABAergic tone.ConclusionsThese findings, together, underscore that Cajal–Retzius cells contribute to the ethanol‐induced aberration of cortical development and abnormal GABAergic neurotransmission at the impactful time when intracortical circuits form.