ArticleJournal of neuroinflammation2020
TREM-2-p38 MAPK signaling regulates neuroinflammation during chronic cerebral hypoperfusion combined with diabetes mellitus.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 77 citations in OpenAlex.
- Metabolic reprogramming in diabetic panvascular disease: Molecular mechanism and therapeutic strategies.iScience · 2026Review
- STAT6 Targets the Autophagy Pathway to Regulate Microglial Senescence in Cognitive Impairment Caused by Cerebral Small-Vessel Disease.Neuromolecular medicine · 2026Article
- Sex differences in cerebrovascular function across an aerobic exercise intervention in older adults using MRI: Results from the Brain in Motion study.Physiological reports · 2026Article
- Parkinson's disease: spatiotemporal regulation and therapeutic prospects of TREM2-mediated microglial responses.NPJ Parkinson's disease · 2026Review
- cGAMP Enhances Microglial/Macrophage Phagocytosis in Ischemic Stroke Via Activation of the TREM2-DAP10-PI3K Pathway.Inflammation · 2026Article
- Associations of serum sTREM-1 and sTREM-2 with mortality and neurological prognosis in patients resuscitated from cardiac arrest: a machine learning-based approach.Frontiers in medicine · 2026Article
- Macrophage plasticity and metabolic control in muscle repair and disease.Frontiers in immunology · 2026Review
- Impact of Diabetes on Oxidative Stress, Mitochondrial Function, and Neurological Outcomes Following Ischemic Stroke: A Sex-Based Experimental Analysis.Molecular neurobiology · 2025Article
- COG1410 Alleviated Chronic Sleep Deprivation-Induced Memory Loss by Regulating Microglial Phagocytosis and Inhibiting Hippocampal Inflammation.ACS chemical neuroscience · 2025Article
- Daqinjiao Decoction Ameliorates CSVD via RXR-γ/PPAR-γ/VEGF-α Pathway: Insights From Transcriptome Sequencing and Network Pharmacology.Journal of cellular and molecular medicine · 2025Article
- TREM2 deficiency exacerbates cognitive impairment by aggravating α-Synuclein-induced lysosomal dysfunction in Parkinson's disease.Cell death discovery · 2025Article
- Foamy macrophages in atherosclerosis: unraveling the balance between pro- and anti-inflammatory roles in disease progression.Frontiers in cardiovascular medicine · 2025Review
- ADAM17 Inhibition Protects Cognition in Intermittent Hypoxia: The Role of TREM2.Nature and science of sleep · 2025Article
- TREM2Frontiers in immunology · 2025Review
- Trem2 acts as a non-classical receptor of interleukin-4 to promote diabetic wound healing.Clinical and translational medicine · 2024Article
- Orthostatic Hypotension Promotes the Progression From Mild Cognitive Impairment to Dementia in Type 2 Diabetes Mellitus.The Journal of clinical endocrinology and metabolism · 2024Article
- Boosting Microglial Lipid Metabolism via TREM2 Signaling by Biomimetic Nanoparticles to Attenuate the Sevoflurane-Induced Developmental Neurotoxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Functional BRI2-TREM2 interactions in microglia: implications for Alzheimer's and related dementias.EMBO reports · 2024Article
- TREM2 improves microglia function and synaptic development in autism spectrum disorders by regulating P38 MAPK signaling pathway.Molecular brain · 2024Article
- Mitigating neurodegenerative diseases: the protective influence of baicalin and baicalein through neuroinflammation regulation.Frontiers in pharmacology · 2024Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundDiabetes mellitus (DM) and chronic cerebral hypoperfusion(CCH)are both risk factors for cognitive impairment. However, whether DM and CCH can synergistically promote cognitive impairment and the related pathological mechanisms remain unknown.
methodsTo investigate the effect of DM and CCH on cognitive function, rats fed with high-fat diet (HFD) and injected with low-dose streptozotocin (STZ) followed by bilateral common carotid artery occlusion (BCCAO) were induced to mimic DM and CCH in vivo and mouse BV2 microglial cells were exposed to hypoxia and/or high glucose to mimic CCH complicated with DM pathologies in vitro. To further explore the underlying mechanism, TREM-2-specific small interfering RNA and TREM-2 overexpression lentivirus were used to knock out and overexpress TREM-2, respectively.
resultsCognitive deficits, neuronal cell death, neuroinflammation with microglial activation, and TREM-2-MAPK signaling were enhanced when DM was superimposed on CCH both in vivo and in vitro. Manipulating TREM-2 expression levels markedly regulated the p38 MAPK signaling and the inflammatory response in vitro. TREM-2 knockout intensified while TREM-2 overexpression suppressed the p38 MAPK signaling and subsequent pro-inflammatory mediator production under high glucose and hypoxia condition.
conclusionsThese results suggest that TREM-2 negatively regulates p38 MAPK-mediated inflammatory response when DM was synergistically superimposed on CCH and highlight the importance of TREM-2 as a potential target of immune regulation in DM and CCH.
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