Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD, Buenos Aires, Argentina.
Neurotox Res. 2010 Jul;18(1):69-81. doi: 10.1007/s12640-009-9132-z. Epub 2009 Nov 20.
The development of the central nervous system can be permanently affected by insults received during the perinatal period, predisposing the organism to long-term behavioral and neurochemical abnormalities. Rats exposed to different types of stress during the last week of gestation produce offspring that show several alterations, many of which have been attributed to changes in dopamine (DA) neurotransmission that could serve as the neurochemical basis for the development of neuropsychiatric disorders. Employing an immunocytochemical approach, we studied the expression levels of two transcription factors Nurr1 and Pitx3 which are expressed at critical moments of DA neurons differentiation as well as the expression of the rate limiting enzyme in DA synthesis, tyrosine hydroxylase (TH) in mesencephalic areas of the brains of prenatally stressed (PS) offspring at different postnatal ages. Main results show that stress exerted to the gestant mother produces permanent effect in the ontogenetic expression of key factors related to the DA metabolism mainly in the ventral tegmental area (VTA) of the mesencephalon. The immunocytochemical expression of the transcription factor Nurr1 shows an increase at postnatal days (PNDs) 7, 28, and 60 whereas Pitx3 shows a decrease at PND 28 and an increase at 60 PND. The rate limiting step in DA synthesis, the enzyme TH shows a decrease at PND 7 to reach control levels at PNDs 28 and 60. The increase of TFs might be up-regulating TH in order to restore DA levels that were previously seen to be normal before puberty. The area selectivity of the increase of the TFs toward VTA and the mesolimbic pathway indicates that an insult received during the prenatal period will exert mainly motivational, emotional, and reward behavior impairments in the adult life.
中枢神经系统的发育可能会因围产期受到的损伤而永久受到影响，使机体容易出现长期的行为和神经化学异常。在妊娠最后一周接受不同类型应激的大鼠会产生后代，这些后代表现出多种改变，其中许多改变归因于多巴胺（DA）神经传递的变化，这可能是神经精神障碍发展的神经化学基础。我们采用免疫细胞化学方法研究了两个转录因子 Nurr1 和 Pitx3 的表达水平，它们在 DA 神经元分化的关键时期表达，以及限速酶 DA 合成中的酪氨酸羟化酶（TH）在产前应激（PS）后代中脑的中脑区域的表达水平。主要结果表明，对妊娠母体施加的应激会对与 DA 代谢相关的关键因素的个体发育表达产生永久影响，主要在中脑的腹侧被盖区（VTA）。转录因子 Nurr1 的免疫细胞化学表达在出生后第 7、28 和 60 天增加，而 Pitx3 在第 28 天减少，在第 60 天增加。DA 合成的限速酶 TH 在第 7 天减少，在第 28 和 60 天达到对照水平。TFs 的增加可能是上调 TH，以恢复青春期前正常的 DA 水平。TFs 对 VTA 和中边缘通路的增加具有区域选择性，表明产前时期受到的损伤将在成年期主要对动机、情感和奖励行为造成损害。
