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

• Published in: iScience 2023-04, Vol.26 (4), p.106545-106545, Article 106545
• Main Authors: Selles, Maria Clara, Fortuna, Juliana T.S., de Faria, Yasmin P.R., Siqueira, Luciana Domett, Lima-Filho, Ricardo, Longo, Beatriz M., Froemke, Robert C., Chao, Moses V., Ferreira, Sergio T.
• Format: Article
• Language: English
• Subjects: Immunology; Molecular physiology; Neuroscience
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.106545

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. [Display omitted] •Oxytocin expression is downregulated in Alzheimer’s disease models•Intranasal oxytocin increases hippocampal oxytocin immunoreactivity•Oxytocin attenuates Alzheimer’s disease-related microglial activation•Intranasal oxytocin reverses social and non-social memory deficits in APP/PS1 mice Molecular physiology; Neuroscience; Immunology