Evidence map›Paper›PMID 37072932›Full record

ArticleCNS neuroscience & therapeutics2023

Preferential pruning of inhibitory synapses by microglia contributes to alteration of the balance between excitatory and inhibitory synapses in the hippocampus in temporal lobe epilepsy.

Jianchen Fan, Xinyan Dong, Yejiao Tang, Xuehui Wang, Donghui Lin, Lifen Gong, Chen Chen, Jie Jiang, Weida Shen, Anyu Xu and 4 more

Open access · goldAbstract read
In one paragraph

Article in CNS neuroscience & therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
4.1field-weighted citation impact, top 5% of its field
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

29 citing papers in PubMed, 33 citations in OpenAlex.

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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

14 authors at 4 institutions in 2 countries.

Jianchen FanCollege of Pharmaceutical Sciences, Institute of Pharmacology and Toxicology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang University, Hangzhou, China.
Xinyan DongDepartment of Neurology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center For Child Health, Hangzhou, China.
Yejiao TangCollege of Pharmaceutical Sciences, Institute of Pharmacology and Toxicology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang University, Hangzhou, China.
Xuehui WangDepartment of Neurology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center For Child Health, Hangzhou, China.
Donghui LinDepartment of Neurology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center For Child Health, Hangzhou, China.
Lifen GongDepartment of Neurology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center For Child Health, Hangzhou, China.
Chen ChenDepartment of Neurology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center For Child Health, Hangzhou, China.
Jie JiangDepartment of Neurology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center For Child Health, Hangzhou, China.
Weida ShenKey Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, China.
Anyu XuKey Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, China.
Xiangnan ZhangCollege of Pharmaceutical Sciences, Institute of Pharmacology and Toxicology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang University, Hangzhou, China.
Yicheng XieDepartment of Neurology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center For Child Health, Hangzhou, China.ORCID 0000-0001-9879-8513
Xin HuangDepartment of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Linghui ZengCollege of Pharmaceutical Sciences, Institute of Pharmacology and Toxicology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang University, Hangzhou, China.ORCID 0000-0002-5924-4419
Children's Hospital of Zhejiang University · CNMinistry of Education · NZHangzhou City UniversityFirst Affiliated Hospital Zhejiang University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA consensus has formed that neural circuits in the brain underlie the pathogenesis of temporal lobe epilepsy (TLE). In particular, the synaptic excitation/inhibition balance (E/I balance) has been implicated in shifting towards elevated excitation during the development of TLE.

methodsSprague Dawley (SD) rats were intraperitoneally subjected to kainic acid (KA) to generate a model of TLE. Next, electroencephalography (EEG) recording was applied to verify the stability and detectability of spontaneous recurrent seizures (SRS) in rats. Moreover, hippocampal slices from rats and patients with mesial temporal lobe epilepsy (mTLE) were assessed using immunofluorescence to determine the alterations of excitatory and inhibitory synapses and microglial phagocytosis.

resultsWe found that KA induced stable SRSs 14 days after status epilepticus (SE) onset. Furthermore, we discovered a continuous increase in excitatory synapses during epileptogenesis, where the total area of vesicular glutamate transporter 1 (vGluT1) rose considerably in the stratum radiatum (SR) of cornu ammonis 1 (CA1), the stratum lucidum (SL) of CA3, and the polymorphic layer (PML) of the dentate gyrus (DG). In contrast, inhibitory synapses decreased significantly, with the total area of glutamate decarboxylase 65 (GAD65) in the SL and PML diminishing enormously. Moreover, microglia conducted active synaptic phagocytosis after the formation of SRSs, especially in the SL and PML. Finally, microglia preferentially pruned inhibitory synapses during recurrent seizures in both rat and human hippocampal slices, which contributed to the synaptic alteration in hippocampal subregions.

conclusionsOur findings elaborately characterize the alteration of neural circuits and demonstrate the selectivity of synaptic phagocytosis mediated by microglia in TLE, which could strengthen the comprehension of the pathogenesis of TLE and inspire potential therapeutic targets for epilepsy treatment.

Indexed as

Epilepsy, Temporal LobeAnimalsCA1 Region, HippocampalDisease Models, AnimalHippocampusHumansKainic AcidMicrogliaRatsRats, Sprague-DawleySeizuresSynapsesKainic AcidE/I balanceepilepsymicrogliasynapsesynaptic phagocytosis

Identifiers

PMID37072932
PMCPMC10493672
OpenAlexW4366351846

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.