ArticleGenes & diseases2022
Hippocampal overexpression of TREM2 ameliorates high fat diet induced cognitive impairment and modulates phenotypic polarization of the microglia.
Article in Genes & diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Effects of diabetes on microglial physiology: a systematic review of in vitro, preclinical and clinical studies.Journal of neuroinflammation · 2023Pooled it
- Diabetes-Associated Cognitive Impairment: Pathophysiology and Emerging Therapies.Annals of clinical and translational neurology · 2026Review
- GHSR suppression in neurons protects against aging-associated metabolic and cognitive impairments.GeroScience · 2026Article
- Intergenerational inheritance of paternal metabolic disorder: miR-29a/c-3p/glucose-6-phosphatase 1 axis in glucose intolerance propagation.Cellular and molecular life sciences : CMLS · 2026Article
- TREM2 in neurodegenerative diseases and acute neurological injuries: mechanisms to targeted therapies.Cell communication and signaling : CCS · 2026Review
- β-Asarone Mediates the Alleviation of Neuroinflammation in Alzheimer's Disease Via Modulation of the TREM2/PI3K/AKT Signaling Pathway.Inflammation · 2026Article
- High‑fat diet and cognitive dysfunction: Mechanistic insights into diet‑induced neurodegeneration (Review).International journal of molecular medicine · 2026Review
- Microglial NFAT5 aggravates neuroinflammation via mediating NLRP6 inflammasome in experimental ischemic stroke.Genes & diseases · 2025Article
- Microglia sensing of peripheral signals that bridge the brain and body.Molecular neurodegeneration · 2025Review
- Nobiletin (NOB) nanoparticles ameliorate chronic paradoxical sleep deprivation (PSD)-induced cognitive deficits in rats.Cell death discovery · 2025Article
- Microglial Dysfunction and Amyloid-Beta Pathology in Alzheimer's Disease and HIV-Associated Neurocognitive Disorders.International journal of molecular sciences · 2025Review
- Article
- Risk Factors, Pathological Changes, and Potential Treatment of Diabetes-Associated Cognitive Dysfunction.Journal of diabetes · 2025Review
- Microglia, Trem2, and Neurodegeneration.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025Review
- Metabolic stress and age drive inflammation and cognitive decline in mice and humans.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Dapagliflozin Improves High-Fat Diet-Induced Cognitive Impairment in Female Mice.Brain and behavior · 2025Article
- Microglial TREM2 and cognitive impairment: insights from Alzheimer's disease with implications for spinal cord injury and AI-assisted therapeutics.Frontiers in cellular neuroscience · 2025Review
- Effect and mechanism of GLP-1 on cognitive function in diabetes mellitus.Frontiers in neuroscience · 2025Review
- TREM2Frontiers in immunology · 2025Review
- A High-Carbohydrate Diet Induces Cognitive Impairment and Promotes Amyloid Burden and Tau Phosphorylation via PI3K/Akt/GSK-3β Pathway in db/db Mice.Biomedicines · 2024Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) share several common pathophysiological features. Rare variants of triggering receptor expressed on myeloid cells 2 (TREM2) increase the risk of developing AD, suggesting the involvement of TREM2 and innate immunity in AD development. It is still unknown whether TREM2 is related to cognitive impairment in T2DM. Here, we investigated the effects of the hippocampal overexpression of TREM2 on cognitive in long-term high-fat diet (HFD)-fed mice. Male C57BL/6J mice were maintained on HFD for 50 weeks. TREM2 was overexpressed in the hippocampus 36 weeks after HFD feeding using adeno-associated virus vector (AAV)-mediated gene delivery. The results showed that the HFD feeding induced rapid and persistent weight gain, glucose intolerance and significant impairments in learning and memory. Compared with AAV-con, AAV-TREM2 significantly ameliorated cognitive impairment without altering body weight and glucose homeostasis in HFD mice. The overexpression of TREM2 upregulated the synaptic proteins spinophilin, PSD95 and synaptophysin, suggesting the improvement in synaptic transmission. Dendritic complexity and spine density in the CA1 region were rescued after TREM2 overexpression. Furthermore, TREM2 markedly increased the number of iba-1/Arg-1-positive microglia in the hippocampus, suppressed neuroinflammation and microglial activation. In sum, hippocampal TREM2 plays an important role in improving HFD-induced cognitive dysfunction and promoting microglial polarization towards the M2 anti-inflammatory phenotype. Our study also suggests that TREM2 might be a novel target for the intervention of obesity/diabetes-associated cognitive decline.
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Registered trials
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.