Research Paper Volume 12, Issue 6 pp 5469—5478
Intranasal delivery of 9-cis retinoic acid reduces beta-amyloid deposition via inhibiting astrocyte-mediated inflammation
- 1 Department of Neurology, The Fourth Hospital of Harbin Medical University, Harbin, China
- 2 Department of Ultrasonography, The Fourth Hospital of Harbin Medical University, Harbin, China
- 3 Department of Endocrinology, The First Hospital of Jilin University, Changchun, China
- 4 Department of Neurology, The Second Hospital of Heilongjiang Province, Harbin, China
- 5 Department of Neurology, The Second Hospital of Harbin Medical University, Harbin, China
- 6 Department of Neurology, Gongli Hospital of The Second Military Medical University, Shanghai, China
- 7 Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
Received: November 9, 2019 Accepted: January 27, 2020 Published: March 25, 2020https://doi.org/10.18632/aging.102970
How to Cite
Copyright © 2020 Zhao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Alzheimer's disease (AD) is associated with the accumulation and deposition of a beta-amyloid (Αβ) peptide in the brain, resulting in increased neuroinflammation and synaptic dysfunction. Intranasal delivery of targeted drugs to the brain represents a noninvasive pathway that bypasses the blood-brain barrier and minimizes systemic exposure. The aim of this study was to evaluate the therapeutic effect of intranasally delivered 9-cis retinoic acid (RA) on the neuropathology of an AD mouse model. Herein, we observed dramatically decreased Αβ deposition in the brains of amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic mice (APP/PS1) treated intranasally with 9-cis RA for 4 weeks compared to that in the brains of vehicle-treated mice. Importantly, intranasal delivery of 9-cis RA suppressed Αβ-associated astrocyte activation and neuroinflammation and ultimately restored synaptic deficits in APP/PS1 transgenic mice. These results support the critical roles of Αβ-associated neuroinflammation responses to synaptic deficits, particularly during the deposition of Αβ. Our findings provide strong evidence that intranasally delivered 9-cis RA attenuates neuronal dysfunction in an AD mouse model and is a promising therapeutic strategy for the prevention and treatment of AD.