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Intranasal delivery of 9-cis retinoic acid reduces beta-amyloid deposition via inhibiting astrocyte-mediated inflammation.


ABSTRACT: Alzheimer's disease (AD) is associated with the accumulation and deposition of a beta-amyloid (??) 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 ?? 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 ??-associated astrocyte activation and neuroinflammation and ultimately restored synaptic deficits in APP/PS1 transgenic mice. These results support the critical roles of ??-associated neuroinflammation responses to synaptic deficits, particularly during the deposition of ??. 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.

SUBMITTER: Zhao H 

PROVIDER: S-EPMC7138573 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Intranasal delivery of 9-cis retinoic acid reduces beta-amyloid deposition via inhibiting astrocyte-mediated inflammation.

Zhao Hong H   Li Shuo S   Li Zhuo Z   Yang Shuo S   Li Dandan D   Zheng Jiaolin J   Gao Hongmei H   Yun Ling L   Gu YingLi Y   Li Longxuan L   Zhao Jing J   Fu Yuan Y  

Aging 20200325 6


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. H  ...[more]

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