Evidence map›Paper›PMID 41154637›Full record

ArticleBiomolecules2025

Upregulation of GLT-1 Expression Attenuates Neuronal Apoptosis and Cognitive Dysfunction via Inhibiting the CB1-CREB Signaling Pathway in Mice with Traumatic Brain Injury.

Bin Bu, Ruiyao Ma, Chengyu Wang, Shukun Jiang, Xiaoming Xu

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In one paragraph

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

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0cells of the map it votes in
2citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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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

5 authors.

Bin BuDepartment of Forensic Clinical Medicine, School of Forensic Medicine, China Medical University, Shenyang 110122, China.
Ruiyao MaFirst Clinical College, China Medical University, Shenyang 110001, China.
Chengyu WangDepartment of Forensic Clinical Medicine, School of Forensic Medicine, China Medical University, Shenyang 110122, China.
Shukun JiangDepartment of Forensic Clinical Medicine, School of Forensic Medicine, China Medical University, Shenyang 110122, China.
Xiaoming XuDepartment of Forensic Clinical Medicine, School of Forensic Medicine, China Medical University, Shenyang 110122, China.

Funding

the Key Laboratory of Forensic Bio-evidence Science of Liaoning Province 2023-PYKT-004)the project of the Education Department of Liaoning Province JYTMS20230126
6 · The paper itself

Abstract

backgroundGlutamate transporter 1 (GLT-1) plays a vital role in maintaining glutamate homeostasis in the body. A decreased GLT-1 expression in astrocytes can heighten neuronal sensitivity to glutamate excitotoxicity after traumatic brain injury (TBI). Despite its significance, the mechanisms behind the reduced expression of GLT-1 following TBI remain poorly understood. After TBI, the endocannabinoid 2-arachidonoyl glycerol (2-AG) is elevated several times. 2-AG is known to inhibit key positive transcriptional regulators of GLT-1. This study aims to investigate the role of 2-AG in regulating GLT-1 expression and to uncover the underlying mechanisms involved.

methodsA controlled cortical impact (CCI) model was used to establish a TBI model in C57BL/6J mice. The CB1 receptor antagonist (referred to as AM281) and the monoacylglycerol lipase (MAGL) inhibitor (referred to as JZL184) were administered to investigate the role and mechanism of 2-AG in regulating GLT-1 expression following TBI. Behavioral tests were conducted to assess neurological functions, including the open field, Y-maze, and novel object recognition tests. Apoptotic cells were identified using the TUNEL assay, while Western blot analysis and immunofluorescence were employed to determine protein expression levels.

resultsThe expression of GLT-1 in the contused cortex and hippocampus following TBI showed an initial decrease, followed by a gradual recovery. It began to decrease within half an hour, reached its lowest level at 2 h, and then gradually increased, returning to normal levels by 7 days. The administration of AM281 alleviated neuronal death, improved cognitive function, and reversed the reduction of GLT-1 caused by TBI in vivo. Furthermore, 2-AG decreased GLT-1 expression in astrocytes through the CB1-CREB signaling pathway. Mechanistically, 2-AG activated CB1, which inhibited CREB phosphorylation in astrocytes. This decreased GLT-1 levels and ultimately increased neuronal sensitivity to glutamate excitotoxicity.

conclusionsOur research demonstrated that the upregulation of GLT-1 expression effectively mitigated neuronal apoptosis and cognitive dysfunction by inhibiting the CB1-CREB signaling pathway. This finding may offer a promising therapeutic strategy for TBI.

Indexed as

ApoptosisBrain Injuries, TraumaticCognitive DysfunctionCyclic AMP Response Element-Binding ProteinExcitatory Amino Acid Transporter 2NeuronsReceptor, Cannabinoid, CB1AnimalsArachidonic AcidsDisease Models, AnimalEndocannabinoidsGlyceridesMaleMiceMice, Inbred C57BLSignal TransductionArachidonic AcidsCreb1 protein, mouseCyclic AMP Response Element-Binding ProteinEndocannabinoidsExcitatory Amino Acid Transporter 2Glyceridesglyceryl 2-arachidonateReceptor, Cannabinoid, CB1Slc1a2 protein, mouse2-AGastrocyteCREBGLT-1TBI

Identifiers

PMID41154637
PMCPMC12563142

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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.