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脑损伤后星形胶质细胞的芳香化酶表达:对脑修复中局部雌激素形成的影响。

Aromatase expression by astrocytes after brain injury: implications for local estrogen formation in brain repair.

作者信息

Garcia-Segura L M, Wozniak A, Azcoitia I, Rodriguez J R, Hutchison R E, Hutchison J B

机构信息

MRC Neuroendocrine Development and Behaviour Group, The Barbraham Institute, Cambridge, UK.

出版信息

Neuroscience. 1999 Mar;89(2):567-78. doi: 10.1016/s0306-4522(98)00340-6.

DOI:10.1016/s0306-4522(98)00340-6
PMID:10077336
Abstract

Recent evidence indicates that 17beta-estradiol may have neuroprotective and neuroregenerative properties. Estradiol is formed locally in neural tissue from precursor androgens. The expression of aromatase, the enzyme that catalyses the conversion of androgens to estrogens, is restricted, under normal circumstances, to specific neuronal populations. These neurons are located in brain areas in which local estrogen formation may be involved in neuroendocrine control and in the modulation of reproductive or sex dimorphic behaviours. In this study the distribution of aromatase immunoreactivity has been assessed in the brain of mice and rats after a neurotoxic lesion induced by the systemic administration of kainic acid. This treatment resulted in the induction of aromatase expression by reactive glia in the hippocampus and in other brain areas that are affected by kainic acid. The reactive glia were identified as astrocytes by co-localization of aromatase with glial fibrillary acidic protein and by ultrastructural analysis. No immunoreactive astrocytes were detected in control animals. The same result, the de novo induction of aromatase expression in reactive astrocytes on the hippocampus, was observed after a penetrating brain injury. Furthermore, using a 3H2O assay, aromatase activity was found to increase significantly in the injured hippocampus. These findings indicate that although astrocytes do not normally express aromatase, the enzyme expression is induced in these glial cells by different forms of brain injury. The results suggest a role for local astroglial estrogen formation in brain repair.

摘要

最近的证据表明,17β-雌二醇可能具有神经保护和神经再生特性。雌二醇由前体雄激素在神经组织中局部形成。芳香化酶是催化雄激素转化为雌激素的酶,在正常情况下,其表达仅限于特定的神经元群体。这些神经元位于脑区,在这些脑区中局部雌激素的形成可能参与神经内分泌控制以及生殖或性别二态性行为的调节。在本研究中,评估了在全身给予 kainic 酸诱导神经毒性损伤后小鼠和大鼠脑中芳香化酶免疫反应性的分布。这种处理导致海马体和其他受 kainic 酸影响的脑区中反应性胶质细胞诱导芳香化酶表达。通过芳香化酶与胶质纤维酸性蛋白的共定位以及超微结构分析,将反应性胶质细胞鉴定为星形胶质细胞。在对照动物中未检测到免疫反应性星形胶质细胞。在穿透性脑损伤后也观察到了相同的结果,即海马体中反应性星形胶质细胞中芳香化酶表达的从头诱导。此外,使用 3H2O 测定法,发现受伤海马体中的芳香化酶活性显著增加。这些发现表明,尽管星形胶质细胞通常不表达芳香化酶,但在不同形式的脑损伤后,这些胶质细胞中会诱导该酶的表达。结果提示局部星形胶质细胞雌激素形成在脑修复中发挥作用。

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