Central activation of alpha7 nicotinic signaling attenuates lps-induced neuroinflammation and sickness behavior in adult but not in aged animals
EntityUAM. Departamento de Farmacología; Instituto Teófilo Hernando de I+D del Medicamento (ITH)
PublisherMDPI, Basel, Switzerland
10.3390/molecules26082107Molecules 26.8 (2021): 2107
Funded byThis work was supported by the Spanish Ministry of Science, innovation and Universities Ref. SAF2015-63935-R and Ref. RTI2018-095793-B-I00 and General Council for Research and Innovation of the Community of Madrid and European Structural Funds Ref. B2017/BMD–3827–NRF24ADCM to M.G.L. Aging studies were supported by an NIA grant (R01-AG-033028) to J.P.G .
ProjectGobierno de España. SAF2015-63935-R; Gobierno de España. RTI2018-095793-B-I00; Comunidad de Madrid. B2017/BMD–3827/NRF24AD
SubjectsAgeing; Alpha7 nicotinic receptor; Lipopolysaccharide; Microglia; Neuroinflammation; Farmacia
Rights© 2021 The authors.
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
We previously reported that lipopolysaccharide (LPS) challenge caused microglial-mediated neuroinflammation and sickness behavior that was amplified in aged mice. As α7 nAChRs are im-plicated 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 (intracerebroven-tricular) 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.
Google Scholar:Navarro, Elisa - Norden, Diana M. - Trojanowski, Paige J. - Godbout, Jonathan P. - López, Manuela G.
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