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首页> 外文期刊>The European Journal of Neuroscience >Prenatal inhibition of the kynurenine pathway leads to structural changes in the hippocampus of adult rat offspring
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Prenatal inhibition of the kynurenine pathway leads to structural changes in the hippocampus of adult rat offspring

机译:产前抑制犬尿氨酸途径导致成年大鼠后代海马结构改变

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Glutamate receptors for N-methyl-d-aspartate (NMDA) are involved in early brain development. The kynurenine pathway of tryptophan metabolism includes the NMDA receptor agonist quinolinic acid and the antagonist kynurenic acid. We now report that prenatal inhibition of the pathway in rats with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulphonamide (Ro61-8048) produces marked changes in hippocampal neuron morphology, spine density and the immunocytochemical localisation of developmental proteins in the offspring at postnatal day 60. Golgi-Cox silver staining revealed decreased overall numbers and lengths of CA1 basal dendrites and secondary basal dendrites, together with fewer basal dendritic spines and less overall dendritic complexity in the basal arbour. Fewer dendrites and less complexity were also noted in the dentate gyrus granule cells. More neurons containing the nuclear marker NeuN and the developmental protein sonic hedgehog were detected in the CA1 region and dentate gyrus. Staining for doublecortin revealed fewer newly generated granule cells bearing extended dendritic processes. The number of neuron terminals staining for vesicular glutamate transporter (VGLUT)-1 and VGLUT-2 was increased by Ro61-8048, with no change in expression of vesicular GABA transporter or its co-localisation with vesicle-associated membrane protein-1. These data support the view that constitutive kynurenine metabolism normally plays a role in early embryonic brain development, and that interfering with it has profound consequences for neuronal structure and morphology, lasting into adulthood.
机译:N-甲基-d-天冬氨酸(NMDA)的谷氨酸受体参与早期的大脑发育。色氨酸代谢的犬尿氨酸途径包括NMDA受体激动剂喹啉酸和拮抗剂犬尿酸。我们现在报道在3,4-二甲氧基-N- [4-(3-硝基苯基)噻唑-2-基]苯磺酰胺(Ro61-8048)大鼠的产前通路抑制产生海马神经元形态,脊柱密度的明显变化以及出生后第60天后代中发育蛋白的免疫细胞化学定位。高尔基-柯克斯银染色显示,CA1基础树突和次生基础树突的总数和长度减少,基础树突棘较少,基底乔木的总体树突复杂性降低。在齿状回颗粒细胞中还注意到较少的树突和较少的复杂性。在CA1区和齿状回中发现了更多的含有核标记NeuN和发育蛋白的声波刺猬的神经元。对双皮质素的染色显示,新的带有延长树突状过程的颗粒细胞较少。 Ro61-8048增加了囊泡谷氨酸转运蛋白(VGLUT)-1和VGLUT-2的神经元末端染色数量,囊泡GABA转运蛋白的表达或其与囊泡相关膜蛋白1的共定位没有改变。这些数据支持这样的观点,即组成型犬尿氨酸代谢通常在早期胚胎脑发育中起作用,并且干扰它对神经元结构和形态具有深远的影响,一直持续到成年。

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