Oxytocin attenuates microglial activation and restores social and non-social memory in APP/PS1 Alzheimer model mice
Maria Clara Selles,
Juliana T.S. Fortuna,
Yasmin P.R. de Faria,
Luciana Domett Siqueira,
Ricardo Lima-Filho,
Beatriz M. Longo,
Robert C. Froemke,
Moses V. Chao,
Sergio T. Ferreira
Affiliations
Maria Clara Selles
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
Juliana T.S. Fortuna
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil
Yasmin P.R. de Faria
Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil
Luciana Domett Siqueira
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil
Ricardo Lima-Filho
Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil
Beatriz M. Longo
Laboratório de Neurofisiologia, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil
Robert C. Froemke
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; Corresponding author
Moses V. Chao
Skirball Institute for Biomolecular Medicine, New York University Grossman School of Medicine, New York, NY, USA; Corresponding author
Sergio T. Ferreira
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; Corresponding author
Summary: 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.
