ArticleAging2020
CSF1R inhibitor PLX5622 and environmental enrichment additively improve metabolic outcomes in middle-aged female mice.
Article in Aging, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- PLX3397 Reshapes Hepatic Lipid Metabolism Independent of Microglial Depletion.Neuroscience bulletin · 2026Article
- Co-morbid biomarkers for sarcopenic obesity associated with gut microbiota metabolites: From burden to treatment.PLoS computational biology · 2026Article
- Diet gel-based oral drug delivery system for controlled dosing of small molecules for microglia depletion and inducible Cre recombination in mice.Lab animal · 2025Article
- Enriched environment alleviates NLRP3 inflammasome mediated neuroinflammation in diabetes complicated with depression rats.Scientific reports · 2025Article
- Article
- Residual microglia following short-term PLX5622 treatment in 5xFAD mice exhibit diminished NLRP3 inflammasome and mTOR signaling, and enhanced autophagy.Aging cell · 2025Article
- Takeda G protein-coupled receptor 5 (TGR5): an attractive therapeutic target for aging-related cardiovascular diseases.Frontiers in pharmacology · 2025Review
- Environmental Enrichment Improves Motor Function and Muscle Transcriptome of Aged Mice.Advanced biology · 2024Article
- Tyrosine kinases: multifaceted receptors at the intersection of several neurodegenerative disease-associated processes.Frontiers in dementia · 2024Review
- CSF1R inhibition with PLX5622 affects multiple immune cell compartments and induces tissue-specific metabolic effects in lean mice.Diabetologia · 2023Article
- Diesel Exhaust Particle (DEP)-induced glucose intolerance is driven by an intestinal innate immune response and NLRP3 activation in mice.Particle and fibre toxicology · 2023Article
- Pathophysiological basis and promise of experimental therapies for Gulf War Illness, a chronic neuropsychiatric syndrome in veterans.Psychopharmacology · 2023Review
- Social isolation exacerbates diet-induced obesity and peripheral inflammation in young male mice under thermoneutrality.iScience · 2023Article
- Inhibition of colony stimulating factor-1 receptor (CSF-1R) as a potential therapeutic strategy for neurodegenerative diseases: opportunities and challenges.Cellular and molecular life sciences : CMLS · 2022Review
- What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior.Frontiers in cellular neuroscience · 2022Review
- Hypothalamic inflammation in metabolic disorders and aging.Cellular and molecular life sciences : CMLS · 2021Review
- The Impact of Obesity on Microglial Function: Immune, Metabolic and Endocrine Perspectives.Cells · 2021Review
- Colony stimulating factors in the nervous system.Seminars in immunology · 2021Review
- Hypothalamic Microglial Heterogeneity and Signature under High Fat Diet-Induced Inflammation.International journal of molecular sciences · 2021Review
- Conditional genetic deletion of CSF1 receptor in microglia ameliorates the physiopathology of Alzheimer's disease.Alzheimer's research & therapy · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
As the elderly population grows, chronic metabolic dysfunction including obesity and diabetes are becoming increasingly common comorbidities. Hypothalamic inflammation through CNS resident microglia serves as a common pathway between developing obesity and developing systemic aging pathologies. Despite understanding aging as a life-long process involving interactions between individuals and their environment, limited studies address the dynamics of environment interactions with aging or aging therapeutics. We previously demonstrated environmental enrichment (EE) is an effective model for studying improved metabolic health and overall healthspan in mice, which acts through a brain-fat axis. Here we investigated the CSF1R inhibitor PLX5622 (PLX), which depletes microglia, and its effects on metabolic decline in aging in interaction with EE. PLX in combination with EE substantially improved metabolic outcomes in middle-aged female mice over PLX or EE alone. Chronic PLX treatment depleted 75% of microglia from the hypothalamus and reduced markers of inflammation without affecting brain-derived neurotrophic factor levels induced by EE. Adipose tissue remodeling and adipose tissue macrophage modulation were observed in response to CSF1R inhibition, which may contribute to the combined benefits seen in EE with PLX. Our study suggests benefits exist from combined drug and lifestyle interventions in aged animals.
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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.