GLIAL TRANSCRIPTS AND IMMUNE-CHALLENGED GLIA IN THE SUPRACHIASMATIC NUCLEUS OF YOUNG AND AGED MICE
GLIAL TRANSCRIPTS AND IMMUNE-CHALLENGED GLIA IN THE SUPRACHIASMATIC NUCLEUS OF YOUNG AND AGED MICE
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DOI：
10.3109/07420521003681498
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发表时间：
2010-01-01
影响因子：
2.8
通讯作者：
Bentivoglio, Marina
中科院分区：
文献类型：
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作者：
Deng, Xiao-Hua;Bertini, Giuseppe;Bentivoglio, Marina
随着年龄的增长，生物节律经常受到干扰，下丘脑视交叉上核（SCN）中神经胶质细胞的衰老相关变化，需要特别注意。特别是，星形胶质细胞有助于SCN功能，并且衰老与大脑中增加的炎症活动有关，其中小胶质细胞可能特别受影响。在此基础上，我们研究了年轻和老年小鼠SCN中胶质细胞的转录和细胞特征，以及胶质细胞对中枢炎症刺激的反应。实时定量逆转录聚合酶链反应（RT-PCR）用于分析编码星形胶质细胞胶质细胞酸性蛋白和小胶质细胞抗原CD 11b的mRNA的表达。这两个成绩单，在这里调查的SCN的第一次，显着增加，在旧的SCN。胶质细胞表型与免疫组化显示肥大和强烈染色的星形胶质细胞和小胶质细胞在老年SCN。在这两个年龄组中，小胶质细胞分散在整个SCN和星形胶质细胞是突出的腹侧部分，视网膜纤维是致密的;在老年SCN，星形胶质细胞也是众多的背侧部分。脑室内注射干扰素-γ和肿瘤坏死因子-α的混合物或磷酸盐缓冲盐水作为对照后，用体视学细胞计数和共聚焦显微镜评价免疫标记。星形胶质细胞和小胶质细胞活化的细胞因子注射反应的表型特征显着增强，在老年SCN。与年轻的SCN相比，老年人的胶质细胞密度也存在亚区域变化。总而言之，研究结果显示，在老年SCN中，胶质转录物的表达增加，星形胶质细胞和小胶质细胞肥大，以及免疫激发的SCN胶质细胞反应的年龄依赖性变化。因此，这些数据指出神经胶质细胞参与了与衰老相关的生物钟变化。（作者通信：marina. univr.it）
Biological rhythms are frequently disturbed with advancing age, and aging-related changes of glia in the hypothalamic suprachiasmatic nucleus (SCN), the master circadian pacemaker, require special attention. In particular, astrocytes contribute to SCN function, and aging is associated with increased inflammatory activity in the brain, in which microglia could be especially implicated. On this basis, we investigated in the SCN of young and old mice glial transcripts and cell features, and the glial cell response to a central inflammatory challenge. Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was used to analyze the expression of mRNAs encoding the astrocytic glial fibrillary acidic protein and the microglial antigen CD11b. Both these transcripts, here investigated in the SCN for the first time, were significantly increased in the old SCN. Glial cell phenotyping with immunohistochemistry revealed hypertrophic and intensely stained astrocytes and microglia in the aged SCN. In both age groups, microglia were scattered throughout the SCN and astrocytes were prominent in the ventral portion, where retinal fibers are densest; in the aged SCN, astrocytes were also numerous in the dorsal portion. After intracerebroventricular injections of a mixture of interferon-gamma and tumor necrosis factor-alpha, or phosphate-buffered saline as control, immunolabeling was evaluated with stereological cell counts and confocal microscopy. Phenotypic features of astrocyte and microglia activation in response to cytokine injections were markedly enhanced in the aged SCN. Subregional variations in glial cell density were also documented in the aged compared to the young SCN. Altogether, the findings show increases in the expression of glial transcripts and hypertrophy of astrocytes and microglia in the aged SCN, as well as age-dependent variation in the responses of immune-challenged SCN glia. The data thus point out an involvement of glia in aging-related changes of the biological clock. (Author correspondence: marina.bentivoglio@univr.it)