Evidence map›Paper›PMID 42138018›Full record

ArticleCNS neuroscience & therapeutics2026

Targeting mGluR2/3 Signaling With LY341495 Restores Dentate Gyrus Function and Cognitive Performance in a Male Mouse Model of Alzheimer's Disease.

Cui-Ping Chen, Ting Zhang, Er-Deng E, Tian-Yang Xu, Qing Han, Xiang Gao, Jie Sun, Yi Huang, Jian-Hong Yang, Xiao-Qin Zhang

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Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Cui-Ping ChenCerebrovascular Disease Center, Ningbo Key Laboratory of Nervous System and Brain Function, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.ORCID https://orcid.org/0009-0005-0254-855X
Ting ZhangDepartment of Pharmacology, Health Science Center, Ningbo University, Ningbo, Zhejiang, China.
Er-Deng EDepartment of Pharmacology, Health Science Center, Ningbo University, Ningbo, Zhejiang, China.ORCID https://orcid.org/0009-0005-7318-5418
Tian-Yang XuDepartment of Pharmacology, Health Science Center, Ningbo University, Ningbo, Zhejiang, China.
Qing HanCerebrovascular Disease Center, Ningbo Key Laboratory of Nervous System and Brain Function, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
Xiang GaoNingbo Key Laboratory of Nervous System and Brain Function, Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
Jie SunNingbo Key Laboratory of Nervous System and Brain Function, Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
Yi HuangNingbo Key Laboratory of Nervous System and Brain Function, Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.ORCID https://orcid.org/0000-0003-3598-9747
Jian-Hong YangCerebrovascular Disease Center, Ningbo Key Laboratory of Nervous System and Brain Function, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
Xiao-Qin ZhangCerebrovascular Disease Center, Ningbo Key Laboratory of Nervous System and Brain Function, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.ORCID https://orcid.org/0000-0003-0254-7598

Funding

National Natural Science Foundation of China 82201322Ningbo Clinical Research Center for Emergency and Critical Diseases 2024L003Ningbo Science and Technology Project 2023H017Ningbo Top Medical and Health Research Program 2022020304Ningbo Top Medical and Health Research Program 2024010317the Natural Science Foundation of Zhejiang Province LY24H090001
6 · The paper itself

Abstract

backgroundAberrant metabotropic glutamate receptor 2/3 (mGluR2/3) signaling has been implicated in the synaptic and cognitive deficits observed in Alzheimer's disease (AD), yet the underlying regulatory mechanisms remain unclear. This study investigated the therapeutic potential of LY341495, a selective mGluR2/3 antagonist, in APP/PS1 transgenic mice, a widely used AD model.

methodsMale APP/PS1 mice were treated with the selective mGluR2/3 antagonist LY341495. Cognitive performance was evaluated using behavioral tests. Hippocampal dentate gyrus (DG) alterations were examined by immunohistochemistry and electrophysiology, including analyses of mGluR2/3 expression, excitatory synaptic activity, adult neurogenesis, calbindin expression, and amyloid-β plaque burden.

resultsAPP/PS1 mice exhibited pathological upregulation of mGluR2/3 in the DG, accompanied by altered presynaptic glutamatergic transmission, reduced neurogenesis, decreased calbindin expression, and deficits in recognition and spatial memory. LY341495 treatment attenuated the aberrant mGluR2/3 upregulation, enhanced excitatory synaptic activity, and improved calbindin levels and neurogenesis in the DG. Importantly, these changes were associated with significant reductions in DG amyloid-β plaque burden and marked improvements in cognitive performance.

conclusionsThis study highlights the novelty of linking mGluR2/3 inhibition to the restoration of calcium-buffering capacity, as reflected by calbindin expression and neurogenesis, processes critical for DG plasticity and resilience. These findings underscore the therapeutic potential of LY341495 as a novel intervention targeting mGluR2/3 signaling in AD.

Indexed as

Alzheimer DiseaseAmino AcidsDentate GyrusExcitatory Amino Acid AntagonistsReceptors, Metabotropic GlutamateXanthenesAnimalsCognitive EnhancementDisease Models, AnimalMaleMiceMice, TransgenicNeurogenesisSignal TransductionAmino AcidsExcitatory Amino Acid AntagonistsLY 341495metabotropic glutamate receptor 2metabotropic glutamate receptor 3Receptors, Metabotropic GlutamateXanthenesAlzheimer's diseasecognitive deficitsdentate gyrusLY341495metabotropic glutamate receptors

Identifiers

PMID42138018
PMCPMC13176937

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.