Evidence map›Paper›PMID 41075047›Full record

ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2025

TNF-α Inhibition Modulates CX3CR1, Pyroptosis-related Genes, and BDNF to Alleviate Anxiety-like Behavior in Type 2 Diabetic Rats.

Dian Eurike Septyaningtrias, Tri Agusti Sholikah, Saihas Suhda, Yustina Andwi Ari Sumiwi, Rina Susilowati

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Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Dian Eurike SeptyaningtriasDepartment of Histology and Cell Biology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.ORCID http://orcid.org/0000-0001-9392-5480
Tri Agusti SholikahDepartment of Histology and Cell Biology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.ORCID http://orcid.org/0000-0001-7607-5963
Saihas SuhdaDepartment of Histology and Cell Biology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.ORCID http://orcid.org/0000-0001-5109-3786
Yustina Andwi Ari SumiwiDepartment of Histology and Cell Biology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.ORCID http://orcid.org/0000-0001-5576-4081
Rina SusilowatiDepartment of Histology and Cell Biology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia. rina_susilowati@ugm.ac.id.ORCID http://orcid.org/0000-0001-8248-5803

Funding

Academic Excellence Grant from the Directorate of Research Universitas Gadjah Mada 327/UN1/FKKMK/PPKE/PT/2022
6 · The paper itself

Abstract

backgroundType 2 diabetes is strongly associated with neuroinflammation and neurodegeneration in the hippocampus, yet the underlying mechanisms are not fully understood. This study seeks to address this gap by exploring the role of TNF-α in modulating behavior, fractalkine (CX3CL1) signaling, and pyroptosis-related pathways in the hippocampus of streptozotocin (STZ)-nicotinamide (NA)-induced diabetic rats, thereby providing insights into potential therapeutic targets for diabetes-induced neuroinflammation.

methodsMale Sprague–Dawley rats (10–12 weeks old) were assigned to three groups: the etanercept-treated diabetic (DE) group, diabetic control (DC) group, and normal control (NC) group. Type 2 diabetes was induced via intraperitoneal injections of STZ and NA, with fasting blood glucose levels > 200 mg/dL confirming the condition. Etanercept was administered biweekly. Anxiety-like behavior and locomotor activity were evaluated using the open field test. After ten weeks, the rats were sacrificed, and the hippocampal tissues were dissected for immunohistochemical analysis of GFAP, CX3CR1, CX3CL1, BDNF expression, as well as qPCR, to quantify pyroptosis-related gene expression.

resultsTNF-α inhibition through etanercept treatment attenuated anxiety-like behavior, reduced GFAP and CX3CR1 expression, and lowered the levels of pyroptosis-related genes (Il-1b, Il-18, Nlrp3) in the hippocampus of diabetic rats, whereas CX3CL1 expression remained unaffected. Additionally, etanercept treatment increased BDNF expression in the hippocampus, suggesting a potential neuroprotective effect.

conclusionThis study suggests that TNF-α inhibition decreases hippocampal GFAP, CX3CR1, and pyroptosis-related gene expression, while enhancing BDNF. These changes may contribute to reduced anxiety-like behavior, highlighting a potential neuroprotective role of TNF-α inhibition in type 2 diabetes.

Indexed as

AnxietyBrain-Derived Neurotrophic FactorCX3C Chemokine Receptor 1Diabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2EtanerceptPyroptosisTumor Necrosis Factor-alphaAnimalsHippocampusMaleRatsRats, Sprague-DawleyBdnf protein, ratBrain-Derived Neurotrophic FactorCX3C Chemokine Receptor 1CX3CR1 protein, ratEtanerceptTumor Necrosis Factor-alphaBDNFCX3CL1CX3CR1PyroptosisStreptozotocin-induced diabetic ratsTNF-α antagonist

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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.