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纹状体内6-羟基多巴胺损伤对产前应激大鼠腹侧被盖区多巴胺能神经元的影响存在差异。

Intrastriatal 6-OHDA lesion differentially affects dopaminergic neurons in the ventral tegmental area of prenatally stressed rats.

作者信息

Baier Carlos J, Pallarés María Eugenia, Adrover Ezequiela, Katunar María R, Raisman-Vozari Rita, Antonelli Marta C

机构信息

Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD, Buenos Aires, Argentina.

出版信息

Neurotox Res. 2014 Oct;26(3):274-84. doi: 10.1007/s12640-014-9479-7. Epub 2014 Jun 17.

Abstract

Exposure to a variety of stressful events during the last week of pregnancy in rats interferes with the correct progeny development, which in turn leads to delays in motor development, impaired adaptation to stressful conditions, altered sexual behaviour, learning deficits, neuronal development and brain morphology. Many of these alterations have been attributed to changes in dopamine (DA) neurotransmission and occur primarily in the mesolimbic system. We found that prenatally stressed offspring showed higher levels of cells expressing tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and that these cells were more susceptible to a neurochemical insult with 6-hydroxy-DA (6-OHDA) in adulthood. Moreover, prenatally stressed rats presented differences in terms of the number and asymmetry of neuronal nitric oxide synthase-expressing cells in the VTA and nucleus accumbens, respectively. Similar to the results described for TH-expressing cells, the nitrergic systems were differentially regulated after 6-OHDA lesion in control and prenatally stressed rats. These results indicated that prenatal stress affects the dopaminergic and nitrergic systems in the mesolimbic pathway. In addition, we propose that the mesolimbic areas are more susceptible than the motor areas to a neurochemical insult during adult life.

摘要

在大鼠孕期的最后一周暴露于各种应激事件会干扰子代的正常发育,进而导致运动发育延迟、对应激条件的适应能力受损、性行为改变、学习缺陷、神经元发育和脑形态改变。其中许多改变归因于多巴胺(DA)神经传递的变化,且主要发生在中脑边缘系统。我们发现,产前应激的子代在腹侧被盖区(VTA)中表达酪氨酸羟化酶(TH)的细胞水平较高,并且这些细胞在成年后对6-羟基多巴胺(6-OHDA)的神经化学损伤更敏感。此外,产前应激的大鼠在VTA和伏隔核中分别表达神经元型一氧化氮合酶的细胞数量和不对称性方面存在差异。与表达TH的细胞的结果相似,在对照大鼠和产前应激的大鼠中,6-OHDA损伤后,硝化能系统受到不同的调节。这些结果表明,产前应激会影响中脑边缘通路中的多巴胺能和硝化能系统。此外,我们提出,在成年期,中脑边缘区域比运动区域更容易受到神经化学损伤。

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