DISTINCT ACTIVATION PROFILES IN MICROGLIA OF DIFFERENT AGES: A SYSTEMATIC STUDY IN ISOLATED EMBRYONIC TO AGED MICROGLIAL CULTURES
DISTINCT ACTIVATION PROFILES IN MICROGLIA OF DIFFERENT AGES: A SYSTEMATIC STUDY IN ISOLATED EMBRYONIC TO AGED MICROGLIAL CULTURES
复制标题
DOI：
10.1016/j.neuroscience.2013.09.010
复制
发表时间：
2013-12-19
期刊：
影响因子：
3.3
通讯作者：
Todd, K. G.
中科院分区：
文献类型：
--
作者：
Lai, A. Y.;Dibal, C. D.;Todd, K. G.
小胶质细胞与几种与年龄相关的脑部疾病进展有关。然而，尽管小胶质细胞对这些疾病进展的贡献是公认的，但衰老对其内源性细胞特征的影响却受到了有限的关注。事实上，关于小胶质细胞的结构和功能如何随着发育年龄的变化而变化的全面研究尚未开展。在这里，我们描述了胚胎、新生儿、2 - 3月龄、6-8月龄、9-11月龄制备的初级小胶质细胞的功能反应特征。13只15个月大的老鼠。在基础条件下和被5'-三磷酸腺苷（ATP）或脂多糖激活的小胶质细胞中，评估小胶质细胞形态、谷氨酸（GLU）摄取、营养因子和炎症因子的释放。我们发现不同年龄组的小胶质细胞在形态和功能上都是不同的。在ATP激活后，Neo小胶质细胞反应最活跃，上调一氧化氮、肿瘤坏死因子-a和脑源性神经营养因子的释放以及GLU的摄取。这种上调在不同发育年龄的小胶质细胞中未观察到的小胶质细胞-神经元共培养中转化为神经毒性。有趣的是，13 - 15个月大的小胶质细胞表现出与新生小胶质细胞相似的激活特征，而年轻成人和胚胎的小胶质细胞被ATP激活的较少。我们的数据还确定了嘌呤能受体亚型表达的年龄依赖性差异，这有助于神经元存活的调节。综上所述，我们的数据表明，小胶质细胞的激活和嘌呤能受体谱随着发育年龄呈非线性变化，这对于研究小胶质细胞在神经退行性疾病中的作用是一个潜在的重要发现。(C) 2013年由Elsevier Ltd.代表IBRO出版。
Microglia have been implicated in disease progression for several age-related brain disorders. However, while microglia's contribution to the progression of these disorders is accepted, the effect of aging on their endogenous cellular characteristics has received limited attention. In fact, a comprehensive study of how the structure and function of microglia changes as a function of developmental age has yet to be performed. Here, we describe the functional response characteristics of primary microglial cultures prepared from embryonic, neonatal (Neo), 2 3 month-old, 6-8 month-old, 9-11 month.old, and 13 15 month-old rats. Microglial morphology, glutamate (GLU) uptake, and release of trophic and inflammatory factors were assessed under basal conditions and in microglia activated with adenosine 5'-triphosphate (ATP) or lipopolysaccharide. We found that microglia from different age groups were both morphologically and functionally distinct. Upon activation by ATP, Neo microglia were the most reactive, upregulating nitric oxide, tumor necrosis factor-a, and brain-derived neurotrophic factor release as well as GLU uptake. This upregulation translated into neurotoxicity in microglia-neuron co-cultures that were not observed with microglia of different developmental ages. Interestingly, 13 15 month-old microglia exhibited similar activation profiles to Neo microglia, whereas microglia from younger adults and embryos were activated less by ATP. Our data also identify age-dependent differences in purinergic receptor subtype expression that contribute to the regulation of neuronal survival. Combined, our data demonstrate that microglial activation and purinergic receptor profiles vary non-linearly with developmental age, a potentially important finding for studies examining the role of microglia in neurodegenerative disorders. (C) 2013 Published by Elsevier Ltd. on behalf of IBRO.