小胶质细胞与几种与年龄相关的脑部疾病的疾病进展有关。然而,虽然小胶质细胞对这些疾病进展的贡献是公认的,衰老对其内源性细胞特性的影响受到了有限的关注。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进行。这里,我们描述了从胚胎制备的原代小胶质细胞培养物的功能反应特征,新生儿(Neo),2-3个月大,6-8个月大,9-11个月大,和13-15个月大的老鼠.小胶质细胞形态学,谷氨酸(GLU)摄取,在基础条件下以及用腺苷5'-三磷酸(ATP)或脂多糖激活的小胶质细胞中评估营养和炎症因子的释放。我们发现来自不同年龄段的小胶质细胞在形态和功能上都不同。ATP激活后,新小胶质细胞反应性最强,上调一氧化氮,肿瘤坏死因子-α,和脑源性神经营养因子的释放以及GLU的摄取。这种上调在小胶质细胞-神经元共培养物中转化为神经毒性,而在不同发育年龄的小胶质细胞中未观察到。有趣的是,13-15个月大的小胶质细胞表现出与新小胶质细胞相似的激活曲线,而年轻成人和胚胎的小胶质细胞被ATP激活较少。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,这些差异有助于调节神经元的存活。合并,我们的数据表明,小胶质细胞活化和嘌呤能受体谱随发育年龄非线性变化,研究小胶质细胞在神经退行性疾病中的作用的一个潜在的重要发现。
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), 2-3month-old, 6-8month-old, 9-11month-old, and 13-15month-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-α, 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, 13-15month-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.