Evidence map›Paper›PMID 38570076›Full record

ArticleBrain research bulletin2024

Effects of novel GLT-1 modulator, MC-100093, on neuroinflammatory and neurotrophic biomarkers in mesocorticolimbic brain regions of male alcohol preferring rats exposed chronically to ethanol.

Shelby Travaglianti, Ahmed Alotaibi, Woonyen Wong, Magid Abou-Gharbia, Wayne Childers, Youssef Sari

Open access · goldAbstract read
In one paragraph

Article in Brain research bulletin, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.4field-weighted citation impact, top 12% 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

6 citing papers in PubMed, 9 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

6 authors at 2 institutions in 1 country.

Shelby TravagliantiUniversity of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH 43614, USA.
Ahmed AlotaibiUniversity of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH 43614, USA.
Woonyen WongUniversity of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH 43614, USA.
Magid Abou-GharbiaDepartment of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA 19140, USA.
Wayne ChildersDepartment of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA 19140, USA.
Youssef SariUniversity of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH 43614, USA. Electronic address: youssef.sari@utoledo.edu.
University of Toledo · USTemple University · US

Funding

Novel GLT-1 activators for the treatment of alcohol dependence: preclinical studiesR01AA029674 · NIAAA · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI Magid Abou-Gharbia, YOUSSEF SARI · 2022 to 2026
$2.1M
NIAAA NIH HHS R01 AA029674
6 · The paper itself

Abstract

Chronic ethanol consumption can lead to increased extracellular glutamate concentrations in key reward brain regions, such as medial prefrontal cortex (mPFC) and nucleus accumbens (NAc), and consequently leading to oxidative stress and neuroinflammation. Previous studies from our lab tested β-lactam antibiotics and novel beta-lactam non-antibiotic, MC-100093, and showed these β-lactam upregulated the major astrocytic glutamate transporter, GLT-1, and consequently reduced ethanol intake and normalized glutamate homeostasis. This present study tested the effects of novel synthetic β-lactam non-antibiotic drug, MC-100093, in chronic ethanol intake and neuroinflammatory and trophic factors in subregions of the NAc (NAc core and shell) and mPFC (Prelimbic, PL; and Infralimbic, IL) of male P rats. MC-100093 treatment reduced ethanol intake after 5-week drinking regimen. Importantly, MC-100093 attenuated ethanol-induced downregulation of brain derived neurotrophic factor (BDNF) expression in these brain regions. In addition, MC-100093 attenuated ethanol-induced upregulation of pro-inflammatory cytokines such as TNF-a and HMGB1 in all these brain regions. Furthermore, MC-100093 treatment attenuated ethanol-induced increase in RAGE in these brain regions. MC-100093 prevented neuroinflammation caused by ethanol intake as well as increased neurotrophic factor in mesocorticolimbic brain regions. MC-100093 treatment reduced ethanol intake and this behavioral effect was associated with attenuation of reduced trophic factors and increased pro-inflammatory factors. MC-100093 is considered a small molecule that may have potential therapeutic effects for the treatment of the effects of chronic exposure to ethanol.

Indexed as

EthanolExcitatory Amino Acid Transporter 2Nucleus AccumbensPrefrontal CortexAlcohol DrinkingAlcoholismAnimalsBiomarkersBrainBrain-Derived Neurotrophic FactorMaleNeuroinflammatory DiseasesRatsBiomarkersBrain-Derived Neurotrophic FactorEthanolExcitatory Amino Acid Transporter 2Slc1a2 protein, ratBDNFEthanol dependenceMC-100093NeuroinflammationTNF-α

Identifiers

PMID38570076
PMCPMC11056292
OpenAlexW4393364962

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.