Oxytocin attenuates microglial activation and restores social and non-social memory in APP/PS1 Alzheimer model mice.

Autor:	Selles MC; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.; Skirball Institute for Biomolecular Medicine, New York University Grossman School of Medicine, New York, NY, USA., Fortuna JTS; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil., de Faria YPR; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil., Siqueira LD; Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil., Lima-Filho R; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil., Longo BM; Laboratório de Neurofisiologia, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil., Froemke RC; Skirball Institute for Biomolecular Medicine, New York University Grossman School of Medicine, New York, NY, USA.; Neuroscience Institute and Department of Otolaryngology, New York University Grossman School of Medicine, New York, NY, USA., Chao MV; Skirball Institute for Biomolecular Medicine, New York University Grossman School of Medicine, New York, NY, USA., Ferreira ST; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.; D'Or Institute for Research and Education, Rio de Janeiro, Rio de Janeiro, Brazil.; Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2023 Mar 31; Vol. 26 (4), pp. 106545. Date of Electronic Publication: 2023 Mar 31 (Print Publication: 2023).
DOI:	10.1016/j.isci.2023.106545
Abstrakt:	Alzheimer's disease (AD) is characterized by neurodegeneration, memory loss, and social withdrawal. Brain inflammation has emerged as a key pathogenic mechanism in AD. We hypothesized that oxytocin, a pro-social hypothalamic neuropeptide with anti-inflammatory properties, could have therapeutic actions in AD. Here, we investigated oxytocin expression in experimental models of AD, and evaluated the therapeutic potential of treatment with oxytocin. Amyloid-β peptide oligomers (AβOs) reduced oxytocin expression in vitro and in vivo , and treatment with oxytocin prevented microglial activation induced by AβOs in purified microglial cultures. Treatment of aged APP/PS1 mice, a mouse model of AD, with intranasal oxytocin attenuated microglial activation and favored deposition of Aβ in dense core plaques, a potentially neuroprotective mechanism. Remarkably, treatment with oxytocin alleviated social and non-social memory impairments in aged APP/PS1 mice. Our findings point to oxytocin as a potential therapeutic target to reduce brain inflammation and correct memory deficits in AD. Competing Interests: Authors declare that they have no competing interests. (© 2023 The Author(s).)
Databáze:	MEDLINE
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