Acute and subacute IL-1β administrations differentially modulate neuroimmune and neurotrophic systems: possible implications for neuroprotection and neurodegeneration.
Acute and subacute IL-1β administrations differentially modulate neuroimmune and neurotrophic systems: possible implications for neuroprotection and neurodegeneration.
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DOI：
10.1186/1742-2094-10-59
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发表时间：
2013-05-07
影响因子：
9.3
通讯作者：
Dong Y
中科院分区：
文献类型：
--
作者：
Song C;Zhang Y;Dong Y
在阿尔茨海默病、中风和脑损伤中，激活的小胶质细胞可以释放促炎细胞因子，例如白细胞介素 (IL)-1β。这些细胞因子可能会改变星形胶质细胞和神经营养蛋白的功能，从而影响神经元的存活并诱导细胞凋亡。然而，不同大脑状况下神经炎症和神经营养蛋白功能之间的相互作用尚不清楚。本研究假设急性和亚急性升高的 IL-1β 差异调节神经胶质和神经营养蛋白功能，这与其在神经保护和神经变性中的作用有关。对大鼠进行静脉注射。注射盐水或 IL-1β 1 或 8 天，并在径向迷宫中进行测试。测量海马中胶质细胞标记物、神经营养因子、神经营养因子受体、β-淀粉样前体蛋白（APP）的 mRNA 和蛋白质表达以及促炎和抗炎细胞因子的浓度。与对照组相比，IL-1 给药 4 天后发现记忆缺陷，但 IL-1 受体拮抗剂 (RA) 减弱了这种缺陷。亚急性IL-1给药增加了APP、小胶质细胞活性标志物CD11b和p75神经营养蛋白受体的表达，以及肿瘤坏死因子(TNF)-α和IL-1β的浓度，但降低了星形胶质细胞活性标志物胶质纤维酸性蛋白(GFAP)、脑源性神经营养因子(BDNF)和TrK B的表达。相比之下， 急性 IL-1 给药后发现 NGF、BDNF 和 TrK B 表达上调，这与神经胶质标记物表达和 IL-10 浓度的增加有关。然而，TrK A 在急性 IL-1 给药时下调，在亚急性 IL-1 给药时上调。 IL-1RA 治疗可逆转 IL-1 诱导的亚急性神经胶质细胞活性、细胞因子浓度以及 BDNF 和 p75 表达的变化。这些结果表明，急性和亚急性IL-1给药在急性IL-1给药后诱导不同的神经保护变化，但在亚急性IL-1给药后诱导神经变性。
In Alzheimer’s disease, stroke and brain injuries, activated microglia can release proinflammatory cytokines, such as interleukin (IL)-1β. These cytokines may change astrocyte and neurotrophin functions, which influences neuronal survival and induces apoptosis. However, the interaction between neuroinflammation and neurotrophin functions in different brain conditions is unknown. The present study hypothesized that acute and subacute elevated IL-1β differentially modulates glial and neurotrophin functions, which are related to their role in neuroprotection and neurodegeneration. Rats were i.c.v. injected with saline or IL-1β for 1 or 8 days and tested in a radial maze. mRNA and protein expressions of glial cell markers, neurotrophins, neurotrophin receptors, β-amyloid precursor protein (APP) and the concentrations of pro- and anti-inflammatory cytokines were measured in the hippocampus. When compared to controls, memory deficits were found 4 days after IL-1 administrations, however the deficits were attenuated by IL-1 receptor antagonist (RA). Subacute IL-1 administrations increased expressions of APP, microglial active marker CD11b, and p75 neurotrophin receptor, and the concentration of tumor necrosis factor (TNF)-α and IL-1β, but decreased expressions of astrocyte active marker glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and TrK B. By contrast, up-regulations of NGF, BDNF and TrK B expressions were found after acute IL-1 administration, which are associated with the increase in both glial marker expressions and IL-10 concentrations. However, TrK A was down-regulated by acute and up-regulated by subacute IL-1 administrations. Subacute IL-1-induced changes in the glial activities, cytokine concentrations and expressions of BDNF and p75 were reversed by IL-1RA treatment. These results indicate that acute and subacute IL-1 administrations induce different changes toward neuroprotection after acute IL-1 administrations but neurodegeneration after subacute ones.
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影响因子：
4.7
作者：
Auld, DS;Mennicken, F;Quirion, R
通讯作者：
Quirion, R
影响因子：
9.3
作者：
Griffin, W. Sue T.;Liu, Ling;Barger, Steven W.
通讯作者：
Barger, Steven W.
影响因子：
4.2
作者：
D'Onofrio, Mara;Arisi, Ivan;Cattaneo, Antonino
通讯作者：
Cattaneo, Antonino
影响因子：
2.7
作者：
Gobbo, OL;O'Mara, SM
通讯作者：
O'Mara, SM
DOI：
10.1523/jneurosci.4361-12.2013
发表时间：
2013-03-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Ghosh S;Wu MD;Shaftel SS;Kyrkanides S;LaFerla FM;Olschowka JA;O'Banion MK
通讯作者：
O'Banion MK