Hippocampal CysLT1R overexpression or activation accelerates memory deficits, synaptic dysfunction, and amyloidogenesis in young APP/PS1 transgenic mice.

Content Provider	Europe PMC
Author	Fang, Shun-Chang Wang, Jun-Jie Chen, Fang Tang, Su-Su Mu, Rong-Hao Yuan, Dan-Hua Zhao, Jia-Jia Hong, Hao Long, Yan
Copyright Year	2021
Abstract	BackgroundOur previous studies demonstrated that cysteinyl leukotrienes receptor 1 (CysLT1R) knockout, pharmacological blockade, or hippocampus knockdown produced beneficial effects against Alzheimer’s disease (AD); however, whether CysLT1R upregulation has deleterious effects on AD remains elusive.MethodsIn this study, we investigated the changes in behaviors, hippocampal amyloidogenesis, and synapse plasticity after CysLT1R overexpression by microinfusion of the lentiviral vector, containing its coding sequence of mouse (LV-CysLT1R), into the bilateral dentate gyri (DG) of the hippocampus or CysLT1R activation by repeated systemic administration of its agonist YM-17690 (0.1 mg/kg, once a day, i.p., for 28 d).ResultsThe behavior data showed that overexpression of CysLT1R in hippocampal DG or administration of YM-17690 deteriorated behavioral performance in Morris water maze (MWM), Y-maze tests, and novel object recognition (NOR) in young APP/PS1 mice. The further studies showed that these treatments significantly destroyed synaptic function, as evidenced by impaired hippocampal long-term potentiation (LTP), decreased spine density, low number of synapses, and decreased postsynaptic protein (PSD95), and promoted the generation of amyloid β (Aβ) through increased expression of BACE1 and PS1 in the hippocampus of young APP/PS1 mice.ConclusionsTogether, our results indicate that CysLT1R upregulation accelerates memory impairment in young APP/PS1 mice, which is associated with promoting synaptic dysfunction and amyloidogenesis in the hippocampus.
ISSN	23055839
Volume Number	9
PubMed Central reference number	PMC8576703
Issue Number	20
PubMed reference number	34790737
Journal	Annals of Translational Medicine [Ann Transl Med]
e-ISSN	23055847
DOI	10.21037/atm-21-4518
Language	English
Publisher	AME Publishing Company
Publisher Date	2021-10-01
Access Restriction	Open
Rights License	Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0. 2021 Annals of Translational Medicine. All rights reserved.
Subject Keyword	Cysteinyl leukotrienes receptor 1 (CysLT1R) Alzheimer’s disease (AD) memory synaptic plasticity amyloidogenesis
Content Type	Text
Resource Type	Article
Subject	Medicine