ArticleMolecular neurobiology2024
Experimental Type 2 diabetes and lipotoxicity-associated neuroinflammation involve mitochondrial DNA-mediated cGAS/STING axis: implication of Type-1 interferon response in cognitive impairment.
Article in Molecular neurobiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Mechanisms and Pathogenesis of Diabetic Cognitive Impairment: A Comprehensive Review.Aging and disease · 2025Pooled it
- The cGAS-STING Pathway: A Double-Edged Regulator of Neuroinflammation and Myelin Regeneration.Molecular neurobiology · 2026Review
- Nicotinamide Riboside (NR) Supplementation Exerts Neuroprotective Effects in db/db Mouse Model of Type 2 Diabetes.Journal of molecular neuroscience : MN · 2026Article
- The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- Research Progress on Pathology, Molecular Mechanisms, and Intervention Strategies of Cognitive Dysfunction Associated with Type 2 Diabetes.International journal of general medicine · 2026Review
- Article
- Role of the cGAS-STING signaling pathway in diabetes mellitus and its complications: from mechanisms to therapeutics.Frontiers in pharmacology · 2026Review
- The Role and Therapeutic Potential of the cGAS-STING Signaling Pathway in Alzheimer's Disease.Brain and behavior · 2025Review
- cGAS-STING signaling in brain aging and neurodegeneration: molecular links and therapeutic perspectives.Journal of neuroinflammation · 2025Review
- Cannabidiol Treatment in a Predator-Based Animal Model of PTSD: Assessing Oxidative Stress and Memory Performance.International journal of molecular sciences · 2025Article
- Type 2 Diabetes Mellitus: A Metabolic Model of Accelerated Aging - Multi-Organ Mechanisms and Intervention Approaches.Aging and disease · 2025Review
- Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders.Journal of neuroinflammation · 2025Review
- Exercise Promotes Hippocampal Neurogenesis in T2DM Mice via Irisin/TLR4/MyD88/NF-κB-Mediated Neuroinflammation Pathway.Biology · 2024Article
- Antitumor Potential of Guttiferone E Combined With Carboplatin Against Osimertinib-resistant H1975 Lung Cancer Through Apoptosis.Anticancer research · 2024Article
- Brain-Gut and Microbiota-Gut-Brain Communication in Type-2 Diabetes Linked Alzheimer's Disease.Nutrients · 2024Review
- Cannabidiol and Beta-Caryophyllene Combination Attenuates Diabetic Neuropathy by Inhibiting NLRP3 Inflammasome/NFκB through the AMPK/sirT3/Nrf2 Axis.Biomedicines · 2024Article
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6 authors.
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Abstract
Type-1 IFN (interferon)-associated innate immune response is increasingly getting attention in neurodegenerative and metabolic diseases like type 2 diabetes (T2DM). However, its significance in T2DM/lipotoxicity-induced neuroglia changes and cognitive impairment is missing. The present study aims to evaluate the involvement of cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon gene), IRF3 (interferon regulatory factor-3), TBK (TANK binding kinase)-mediated Type-1 IFN response in the diabetic brain, and lipotoxicity (palmitate-bovine serum albumin conjugate/PA-BSA)-induced changes in cells (neuro2a and BV2). T2DM was induced in C57/BL6 mice by feeding on a high-fat diet (HFD, 60% Kcal) for 16 weeks and injecting a single dose of streptozotocin (100 mg/kg, i.p) in the 12th week. Plasma biochemical parameter analysis, neurobehavioral assessment, protein expression, and quantitative polymerase chain reaction study were carried out to decipher the hypothesis. T2DM-associated metabolic and lipotoxic stress led to mitochondrial impairment causing leakage of mtDNA to the cytoplasm further commencing cGAS activation and its downstream signaling. The diseased hippocampus and cortex showed decreased expression of synaptophysin (p < 0.01) and PSD-95 (p < 0.01, p < 0.05) with increased expression of cGAS (p < 0.001), p-STING (p < 0.001), p-STAT1 (signal transducer and activator of transcription) (p < 0.01), and IFN-β (p < 0.001) compared to normal control. The IFN-β/p-STAT1-mediated microglia activation was executed employing a conditioned media approach. C-176, a selective STING inhibitor, alleviated cGAS/p-STING/IFN-β expression and proinflammatory microglia/M1-associated markers (CD16 expression, CXCL10, TNF-α, IL-1β mRNA fold change) in the diabetic brain. The present study suggests Type-1IFN response may result in neuroglia dyshomeostasis affecting normal brain function. Alleviating STING signaling has the potential to protect T2DM-associated central ailment.
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