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Selective reduction of cerebral cortex GABA neurons in a late gestation model of fetal alcohol spectrum disorder

机译：胎儿酒精谱系障碍晚期妊娠模型中大脑皮质GABA神经元的选择性还原

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Fetal alcohol spectrum disorders (FASD) are associated with cognitive and behavioral deficits, and decreased volume of the whole brain and cerebral cortex. Rodent models have shown that early postnatal treatments, which mimic ethanol toxicity in the third trimester of human pregnancy, acutely induce widespread apoptotic neuronal degeneration and permanent behavioral deficits. However, the lasting cellular and anatomical effects of early ethanol treatments are still incompletely understood. This study examined changes in neocortex volume, thickness, and cellular organization that persist in adult mice after postnatal day 7 (P7) ethanol treatment. Post mortem brain volumes, measured by both MRI within the skull and by fluid displacement of isolated brains, were reduced 10-13% by ethanol treatment. The cerebral cortex showed a similar reduction (12%) caused mainly by lower surface area (9%). In spite of these large changes, several features of cortical organization showed little evidence of change, including cortical thickness, overall neuron size, and laminar organization. Estimates of total neuron number showed a trend level reduction of about 8%, due mainly to reduced cortical volume but unchanged neuron density. However, counts of calretinin (CR) and parvalbumin (PV) subtypes of GABAergic neurons showed a striking >30% reduction of neuron number. Similar ethanol effects were found in male and female mice, and in C57BL/6By and BALB/cJ mouse strains. Our findings indicate that the cortex has substantial capacity to develop normal cytoarchitectonic organization after early postnatal ethanol toxicity, but there is a selective and persistent reduction of GABA cells that may contribute to the lasting cognitive and behavioral deficits in FASD. (C) 2015 Elsevier Inc. All rights reserved.
机译：胎儿酒精频谱异常（FASD）与认知和行为缺陷以及整个大脑和大脑皮层体积减少有关。啮齿动物模型显示，早期的产后治疗模仿人类怀孕晚期的乙醇毒性，可急性诱发广泛的凋亡神经元变性和永久性行为缺陷。然而，早期乙醇治疗的持久细胞和解剖学效果仍不完全清楚。这项研究检查了出生后第7天（P7）乙醇治疗后成年小鼠中新皮质的体积，厚度和细胞组织的变化，这些变化持续存在。通过乙醇处理，通过颅骨内的MRI和孤立的大脑的液体置换测量的验尸后脑容量减少了10-13％。大脑皮层显示出类似的减少（12％），主要是由于较低的表面积（9％）引起的。尽管发生了这些巨大的变化，但皮质组织的一些特征几乎没有变化的迹象，包括皮质厚度，总体神经元大小和层状组织。总神经元数量的估计显示出趋势水平降低了大约8％，这主要是由于皮层体积减少而神经元密度保持不变。但是，GABA能神经元的钙调蛋白（CR）和小白蛋白（PV）亚型的计数显示，神经元数量明显减少了> 30％。在雄性和雌性小鼠以及C57BL / 6By和BALB / cJ小鼠品系中也发现了类似的乙醇作用。我们的发现表明，皮层具有在出生后早期乙醇中毒后发展出正常细胞结构组织的强大能力，但GABA细胞的选择性和持续减少可能有助于FASD的持久认知和行为缺陷。 （C）2015 Elsevier Inc.保留所有权利。

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