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首页> 外文期刊>The European Journal of Neuroscience >Induction of neurogenesis in the adult rat subventricular zone and neostriatum following dopamine D receptor stimulation.
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Induction of neurogenesis in the adult rat subventricular zone and neostriatum following dopamine D receptor stimulation.

机译：多巴胺D受体刺激后，在成年大鼠脑室下区和新纹状体中诱导神经发生。

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Abstract Discrete regions of the adult CNS, including the subventricular zone (SVZ), do retain the capacity for neurogenesis. These progenitor cells may represent a potential new source of cells for replacement therapies in neuroregenerative diseases. An understanding of the microenvironmental signals regulating neurogenesis in the adult brain would facilitate the development of such therapeutic approaches. A particularly strong expression of dopamine D(3) receptor mRNA occurs in the proliferative SVZ during prenatal and early postnatal ontogeny. Although its expression diminishes following development, a restricted D(3) receptor expression persists in this region through adulthood, coincident with continued proliferation in this region. Here, we demonstrate a two-fold induction of cell proliferation (BrdU incorporation) in the SVZ and rostral migratory stream of the adult Sprague-Dawley rat brain following intrasubventricular administration of the dopamine D(3) receptor agonist, 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) for 2 weeks. The number of BrdU-positive cells was elevated ten-fold from very low baseline levels in the neighbouring neostriatum, another region known to express D(3) receptors. These striatal BrdU-positive cells appeared within 3 days following intracerebral infusion of 7-OH-DPAT and were distributed homogeneously throughout the striatum following systemic administration. This suggests that these cells originate from resident progenitor cells rather than the SVZ. Dopamine D(3) receptor activation may serve as a proneuronal differentiation signal as 60-70% of the new cells had neuronal markers following 7-OH-DPAT infusion. These results suggest that the dopamine D(3) receptor may be a good drug target for cell replacement strategies, particularly because of the fact that its expression is almost exclusively limited to the nervous system.
机译：摘要成人中枢神经系统的离散区域，包括脑室下区域（SVZ），确实保留了神经发生的能力。这些祖细胞可能代表了神经再生疾病替代疗法的潜在新细胞来源。对调节成年大脑中神经发生的微环境信号的理解将促进这种治疗方法的发展。多巴胺D（3）受体mRNA的特别强表达发生在产前和产后早期个体发育期间的增生性SVZ中。尽管其表达减少发展后，受限制的D（3）受体表达通过成年在该区域持续存在，与该区域的持续增殖相吻合。在这里，我们证实了多巴胺D（3）受体激动剂7-羟基-N的脑室内给药后，成年Sprague-Dawley大鼠大脑的SVZ和有尾mi游迁移过程中细胞增殖（BrdU掺入）的双重诱导。 N-二正丙基-2-氨基四氢化萘（7-OH-DPAT）持续2周。 BrdU阳性细胞的数量从相邻新纹状体（已知表达D（3）受体的另一个区域）中的极低基线水平提高了十倍。这些纹状体BrdU阳性细胞在脑内注入7-OH-DPAT后3天内出现，并在全身给药后均匀分布在整个纹状体中。这表明这些细胞起源于驻留祖细胞而不是SVZ。多巴胺D（3）受体激活可能充当神经元分化信号，因为60-70％的新细胞在7-OH-DPAT注入后具有神经元标记。这些结果表明，多巴胺D（3）受体可能是细胞替代策略的良好药物靶标，尤其是因为其表达几乎完全限于神经系统这一事实。

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