Evidence map›Paper›PMID 39380368›Full record

ArticleAging cell2025

CaMKIIα-TARPγ8 signaling mediates hippocampal synaptic impairment in aging.

Zhao JianHua, MingCan Li, Qilin Hu, Peter Donoghue, Sanwei Jiang, Junmei Li, Songji Li, Xinyi Ren, Ziyuan Zhang, Jingzhi Du and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Aging cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

The trial behind it

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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

Who cites it

2 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

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

13 authors.

Zhao JianHuaHenan International Joint Research Laboratory of Neurorestoratology for Senile Dementia, Henan Key Laboratory of Neurorestoratology, Department of Neurology, First Affiliated Hospital of Xinxiang Medical University, Weihui, Xinxiang, Henan, China.
MingCan LiHenan International Joint Laboratory of Non-Invasive Neuromodulation, Department of Physiology and Pathophysiology, Xinxiang Medical University, Xinxiang, Henan, China.
Qilin HuHenan International Joint Research Laboratory of Neurorestoratology for Senile Dementia, Henan Key Laboratory of Neurorestoratology, Department of Neurology, First Affiliated Hospital of Xinxiang Medical University, Weihui, Xinxiang, Henan, China.
Peter DonoghueDepartment of Biosciences, Wolfson Research Institute for Health and Wellbeing, Durham University, Durham, UK.
Sanwei JiangHenan International Joint Research Laboratory of Neurorestoratology for Senile Dementia, Henan Key Laboratory of Neurorestoratology, Department of Neurology, First Affiliated Hospital of Xinxiang Medical University, Weihui, Xinxiang, Henan, China.
Junmei LiHenan International Joint Research Laboratory of Neurorestoratology for Senile Dementia, Henan Key Laboratory of Neurorestoratology, Department of Neurology, First Affiliated Hospital of Xinxiang Medical University, Weihui, Xinxiang, Henan, China.
Songji LiHenan International Joint Laboratory of Non-Invasive Neuromodulation, Department of Physiology and Pathophysiology, Xinxiang Medical University, Xinxiang, Henan, China.ORCID 0000-0002-8918-7523
Xinyi RenHenan International Joint Research Laboratory of Neurorestoratology for Senile Dementia, Henan Key Laboratory of Neurorestoratology, Department of Neurology, First Affiliated Hospital of Xinxiang Medical University, Weihui, Xinxiang, Henan, China.
Ziyuan ZhangHenan International Joint Research Laboratory of Neurorestoratology for Senile Dementia, Henan Key Laboratory of Neurorestoratology, Department of Neurology, First Affiliated Hospital of Xinxiang Medical University, Weihui, Xinxiang, Henan, China.
Jingzhi DuHenan International Joint Laboratory of Non-Invasive Neuromodulation, Department of Physiology and Pathophysiology, Xinxiang Medical University, Xinxiang, Henan, China.
Yi YuSchool of Medical Engineering, Xinxiang Medical University, Xinxiang, China.
Paul ChazotDepartment of Biosciences, Wolfson Research Institute for Health and Wellbeing, Durham University, Durham, UK.
Chengbiao LuHenan International Joint Research Laboratory of Neurorestoratology for Senile Dementia, Henan Key Laboratory of Neurorestoratology, Department of Neurology, First Affiliated Hospital of Xinxiang Medical University, Weihui, Xinxiang, Henan, China.ORCID 0000-0001-9074-4430

Funding

Key Scientific Research Projects of Universities of Henan Province 21A310016National Natural Science Foundation of China 81771517Natural Science Foundation of Henan Province 202300410316
6 · The paper itself

Abstract

Aging-related decline in memory and synaptic function are associated with the dysregulation of calcium homeostasis, attributed to the overexpression of voltage-gated calcium channels (VGCC). The membrane insertion of AMPAR governed by the AMPAR auxiliary proteins is essential for synaptic transmission and plasticity (LTP). In this study, we demonstrated the hippocampal expression of the transmembrane AMPAR regulatory proteins γ-8 (TARPγ8) was reduced in aged mice along with the reduced CaMKIIα activity and memory impairment. We further showed that TARPγ8 expression was dependent on CaMKIIα activity. Inhibition of CaMKIIα activity significantly reduced the hippocampal TARPγ8 expression and CA3-CA1 LTP in young mice to a similar level to that of the aged mice. Furthermore, the knockdown of hippocampal TARPγ8 impaired LTP and memory in young mice, which mimicked the aging-related changes. We confirmed the enhanced hippocampal VGCC (Cav-1.3) expression in aged mice and found that inhibition of VGCC activity largely increased both p-CaMKIIα and TARPγ8 expression in aged mice, whereas inhibition of NMDAR or Calpains had no effect. In addition, we found that the exogenous expression of human TARPγ8 in the hippocampus in aged mice restored LTP and memory function. Collectively, these results indicate that the synaptic and cognitive impairment in aging is associated with the downregulation of CaMKIIα-TARPγ8 signaling caused by VGCC activation. Our results suggest that TARPγ8 may be a key molecular biomarker for brain aging and that boosting CaMKIIα-TARPγ8 signaling may be critical for the restoration of synaptic plasticity of aging and aging-related diseases.

Indexed as

AgingCalcium-Calmodulin-Dependent Protein Kinase Type 2HippocampusSignal TransductionAnimalsHumansMaleMiceMice, Inbred C57BLSynapsesCalcium-Calmodulin-Dependent Protein Kinase Type 2agingCaMKIIαhippocampusLTPTARPγ8VGCC

Identifiers

PMID39380368
PMCPMC11709088

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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.