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抗精神病药物治疗后的神经胶质细胞反应性:大鼠实验研究及其对精神病学的意义

Glial reactivity after antipsychotic treatment. An experimental study in rats and its implications for psychiatry.

作者信息

Blázquez Arroyo J L, Fraile Malmierca E, Casadiego Cubides A, Llorca Ramón G, Ledesma Jimeno A

机构信息

Facultad de Medicina, Dpto de Anatomía e Histología Humanas, Avda Alfonso el Sabio s/n. 37007 Salamanca.

出版信息

Actas Esp Psiquiatr. 2010 Sep-Oct;38(5):278-84. Epub 2010 Sep 1.

PMID:21117002
Abstract

INTRODUCTION

The importance of the glial cells in the function of the nervous system and in its pathology has been the object of multiple studies in the last years. Specifically, their role in the action of the antipsychotics is debated. Our study has analyzed glial reactivity in rats treated with antipsychotics.

METHODOLOGY

In a first ultrastructural study of the arcuate nucleus of the hypothalamus, the animals were treated with chlorpromazine for 40 days, and were sacrificed at the end of the treatment, after 20 days of rest without treatment. In another series of studies, with the light microscope and immunohistochemistry we evaluated the immunoreactivity of the glial fibrillary acidic protein (GFAP) in six regions of the central nervous system of rats treated with typical and atypical antipsychotics.

RESULTS

With the electron microscope, the animals treated with chlorpromazine showed a significant reduction of the axosomatic synapses on the neurons of the hypothalamic arcuate nucleus and an increase of glial presence, as noted by the greater amount of astrocyte processes. The mentioned modifications were reversible, tending to normalize in a group of animals sacrificed 20 days after completion of the treatment. In the immunohistochemical study, the glial reaction was important in the territory of the nucleus accumbens with all the antipsychotics, moderate in the cingulate cortex, although only with atypical antipsychotics, and scarcely significant in the rest of the regions.

CONCLUSIONS

Our results confirm that the glial cells are targets of the antipsychotic action, and this will allow us to better understand the action of these drugs and the role of the glial cells in the normal function of the nervous system and in the mental disease.

摘要

引言

近年来,神经胶质细胞在神经系统功能及其病理学中的重要性一直是多项研究的对象。具体而言,它们在抗精神病药物作用中的角色存在争议。我们的研究分析了用抗精神病药物治疗的大鼠的神经胶质反应性。

方法

在对下丘脑弓状核的首次超微结构研究中,动物用氯丙嗪治疗40天,并在治疗结束时、未经治疗休息20天后处死。在另一系列研究中,我们用光学显微镜和免疫组织化学评估了用典型和非典型抗精神病药物治疗的大鼠中枢神经系统六个区域中胶质纤维酸性蛋白(GFAP)的免疫反应性。

结果

在电子显微镜下,用氯丙嗪治疗的动物下丘脑弓状核神经元上的轴体突触显著减少,神经胶质细胞增多,表现为星形胶质细胞突起数量增加。上述改变是可逆的,在治疗结束后20天处死的一组动物中趋于正常化。在免疫组织化学研究中,所有抗精神病药物在伏隔核区域均引起重要的神经胶质反应,在扣带回皮质中反应中等,但仅在使用非典型抗精神病药物时出现,在其他区域几乎无明显反应。

结论

我们的结果证实神经胶质细胞是抗精神病药物作用的靶点,这将使我们能够更好地理解这些药物的作用以及神经胶质细胞在神经系统正常功能和精神疾病中的作用。

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