期刊
MOLECULES
卷 26, 期 8, 页码 -出版社
MDPI
DOI: 10.3390/molecules26082107
关键词
alpha7 nicotinic receptor; neuroinflammation; microglia; lipopolysaccharide; ageing
资金
- Spanish Ministry of Science, innovation and Universities [SAF2015-63935-R, RTI2018-095793-B-I00]
- General Council for Research and Innovation of the Community of Madrid
- European Structural Funds [B2017/BMD-3827NRF24ADCM]
- NIA [R01-AG-033028]
The stimulation of alpha 7 nAChR signaling reduces microglial activation in an in vivo LPS-based model, but this cholinergic-dependent regulation appears to be dysfunctional in microglia of aged mice.
We previously reported that lipopolysaccharide (LPS) challenge caused microglial-mediated neuroinflammation and sickness behavior that was amplified in aged mice. As alpha 7 nAChRs are implicated in the Cholinergic anti-inflammatory pathway, we aimed to determine how alpha 7 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 alpha 7 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 alpha 7 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-1 beta and TNF alpha mRNA levels. Furthermore, central (intracerebroventricular) administration of the alpha 7 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 alpha 7 nAChRs was performed peripherally. Finally, we observed that the positive results of central activation of alpha 7 nAChRs were lost in aged mice. In conclusion, we provide evidence that stimulation of alpha 7 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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