Molecular and cellular characterization of the age-related neuroinflammatory processes occurring in normal rat hippocampus:: potential relation with the loss of somatostatin GABAergic neurons
Molecular and cellular characterization of the age-related neuroinflammatory processes occurring in normal rat hippocampus:: potential relation with the loss of somatostatin GABAergic neurons
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DOI：
10.1111/j.1471-4159.2007.04787.x
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发表时间：
2007-11-01
影响因子：
4.7
通讯作者：
Ruano, Diego
中科院分区：
文献类型：
--
作者：
Gavilan, M. Paz;Revilla, Elisa;Ruano, Diego
在正常的脑老化过程中经常观察到增加的神经炎症反应。然而，在衰老过程中神经炎症和神经退行性变之间的直接联系尚未明确显示。在这里，我们的特点是年龄相关的海马炎症过程和海马神经退行性变的潜在关系。促炎细胞因子IL-1 β和肿瘤坏死因子-α（TNF-α）以及iNOs酶的mRNA表达在老年海马中显著增加。因此，在老年大鼠中观察到许多活化的小胶质细胞。这些细胞差异分布沿着海马，更频繁地位于门和CA 3区。老年大鼠GABA能中间神经元表达的神经肽生长抑素的mRNA表达和生长抑素免疫阳性细胞的数量减少。然而，海马小白蛋白含有GABA能中间神经元的数量被保留。有趣的是，在老年大鼠中，生长抑素和IL-1 β的mRNA表达呈负相关，生长抑素免疫阳性细胞的数量的减少是在齿状回的门比在CA 1区更高。最后，腹腔注射慢性脂多糖（LPS）在年轻的动物模仿年龄相关的海马炎症以及生长抑素mRNA表达的减少。目前的结果强烈支持神经炎症作为一个潜在的因素参与了与年龄相关的生长抑素GABA能细胞的退化。
Increased neuroinflammatory reaction is frequently observed during normal brain aging. However, a direct link between neuroinflammation and neurodegeneration during aging has not yet been clearly shown. Here, we have characterized the age-related hippocampal inflammatory processes and the potential relation with hippocampal neurodegeneration. The mRNA expression of the pro-inflammatory cytokines IL-1 beta and tumor necrosis factor-alpha (TNF-alpha), and the iNOs enzyme was significantly increased in aged hippocampus. Accordingly, numerous activated microglial cells were observed in aged rats. These cells were differentially distributed along the hippocampus, being more frequently located in the hilus and the CA3 area. The mRNA expression of somatostatin, a neuropeptide expressed by some GABAergic interneurons, and the number of somatostatin-immunopositive cells decreased in aged rats. However, the number of hippocampal parvalbumin-containing GABAergic interneurons was preserved. Interestingly, in aged rats, the mRNA expression of somatostatin and IL-1 beta was inversely correlated and, the decrease in the number of somatostatin-immunopositive cells was higher in the hilus of dentate gyrus than in the CA1 region. Finally, intraperitoneal chronic lipopolysaccharide (LPS) injection in young animals mimicked the age-related hippocampal inflammation as well as the decrease of somatostatin mRNA expression. Present results strongly support the neuroinflammation as a potential factor involved in the age-related degeneration of somatostatin GABAergic cells.