Central Activation of Alpha7 Nicotinic Signaling Attenuates LPS-Induced Neuroinflammation and Sickness Behavior in Adult but Not in Aged Animals.
Central Activation of Alpha7 Nicotinic Signaling Attenuates LPS-Induced Neuroinflammation and Sickness Behavior in Adult but Not in Aged Animals.
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Alpha7 烟碱信号传导的中枢激活可减轻成年动物 LPS 诱导的神经炎症和疾病行为，但老年动物则不然。
DOI：
10.3390/molecules26082107
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发表时间：
2021-04-07
期刊：
影响因子：
--
通讯作者：
López MG
中科院分区：
文献类型：
--
作者：
Navarro E;Norden DM;Trojanowski PJ;Godbout JP;López MG
We previously reported that lipopolysaccharide (LPS) challenge caused microglial-mediated neuroinflammation and sickness behavior that was amplified in aged mice. As α7 nAChRs are implicated in the “Cholinergic anti-inflammatory pathway”, we aimed to determine how α7 nAChR stimulation modulates microglial phenotype in an LPS-induced neuroinflammation model in adult and aged mice. For this, BALB/c mice were injected intraperitoneally with LPS (0.33 mg/kg) and treated with the α7 nAChR agonist PNU282987, using different administration protocols. LPS challenge reduced body weight and induced lethargy and social withdrawal in adult mice. Peripheral (intraperitoneal) co-administration of the α7 nAChR agonist PNU282987 with LPS, attenuated body weight loss and sickness behavior associated with LPS challenge in adult mice, and reduced microglial activation with suppression of IL-1β and TNFα mRNA levels. Furthermore, central (intracerebroventricular) administration of the α7 nAChR agonist, even 2 h after LPS injection, attenuated the decrease in social exploratory behavior and microglial activation induced by peripheral administration of LPS, although this recovery was not achieved if activation of α7 nAChRs was performed peripherally. Finally, we observed that the positive results of central activation of α7 nAChRs were lost in aged mice. In conclusion, we provide evidence that stimulation of α7 nAChR signaling reduces microglial activation in an in vivo LPS-based model, but this cholinergic-dependent regulation seems to be dysfunctional in microglia of aged mice.
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DOI：
10.1016/j.pnpbp.2017.01.001
发表时间：
2017-04-03
影响因子：
5.6
作者：
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通讯作者：
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影响因子：
15.1
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Frank-Cannon TC;Alto LT;McAlpine FE;Tansey MG
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Tansey MG
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5.1
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Gao, Tian-Ming
影响因子：
9.3
作者：
De Simone R;Ajmone-Cat MA;Carnevale D;Minghetti L
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影响因子：
4.7
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Han Z;Li L;Wang L;Degos V;Maze M;Su H
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