Effect of aging on the microglial response to peripheral nerve injury
Effect of aging on the microglial response to peripheral nerve injury
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DOI：
10.1016/j.neurobiolaging.2005.07.012
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发表时间：
2006-10-01
影响因子：
4.2
通讯作者：
Streit, Wolfgang J.
中科院分区：
文献类型：
--
作者：
Conde, Jessica R.;Streit, Wolfgang J.
小胶质细胞的形态和免疫表型已被广泛研究，在衰老相关的神经退行性疾病，但在正常的老年中枢神经系统的程度较小，并知之甚少，如何老化影响的能力，小胶质细胞对神经元损伤的反应。本研究的目的是确定老化是否影响小胶质细胞在面神经轴突切断早期反应中的分裂能力。此外，我们研究了在轴突切断术后的时间点小胶质细胞死亡的发生率，以确定衰老是否对小胶质细胞的周转有影响。我们采用DNA标记与H-3-胸苷，TUNEL和凝集素组织化学面神经轴突切断术后，在年轻（3个月），中年（15个月），老年（30个月）Fisher 344-Brown Norway杂交大鼠。损伤后4天，老年大鼠的小胶质细胞增殖仍显著高于年轻大鼠，表明小胶质细胞增殖的调节随年龄的变化而变化。在轴突切断后7、14或21天，小胶质细胞TUNEL染色没有年龄相关的差异。未手术的面核中的凝集素组织化学显示静息小胶质细胞中与衰老相关的形态学变化，包括细胞质肥大和核周染色。尽管老年动物的许多活化小胶质细胞继续表现出密集的核周凝集素反应，但损伤侧活化小胶质细胞的衰老相关差异更为微妙。我们建议，与年龄相关的形态学变化，在老年人的面神经核的增殖反应较少调节可能是小胶质细胞衰老的反映。(c)2005年爱思唯尔公司All rights reserved.
Microglial morphology and immunophenotype have been studied extensively in aging-related neurodegenerative diseases, but to a lesser extent in the normally aged CNS, and little is known about how aging affects the ability of microglia to respond to neuronal injury. The goal of the current study was to determine if aging affects the ability of microglia to divide during the early response to facial nerve axotomy. In addition, we investigated the incidence of microglial cell death during later post-axotomy time points to determine if aging had an effect on microglial turnover. We employed DNA labeling with H-3-thymidine, TUNEL and lectin histochemistry after facial nerve axotomy in young (3 months), middle-aged (15 months), and old (30 months) Fisher344-Brown Norway hybrid rats. Proliferation of microglia in old rats remained significantly higher than in young rats 4 days after injury, suggesting that regulation of microglial proliferation changes with aging. There was no aging-related difference in microglial TUNEL staining at 7, 14 or 21 days post-axotomy. Lectin histochemistry in the unoperated facial nucleus revealed aging-related morphological changes in resting microglia, including hypertrophy of the cytoplasm with dense perinuclear staining. Aging-related differences in activated microglia on the lesioned side were more subtle, although many activated microglia of aged animals continued to exhibit dense perinuclear lectin reactivity. We propose that aging-related changes in morphology in conjunction with a less regulated proliferative response in the aged facial nucleus may be a reflection of microglial senescence. (c) 2005 Elsevier Inc. All rights reserved.