ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2022
Microglia Drive Pockets of Neuroinflammation in Middle Age.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- Cross-species characterisation of microglial morphology and proliferation during ageing.GeroScience · 2026Article
- Distinct Transposable Element Transcript Patterns in Microglia Across Aging and Alzheimer's Disease.Aging cell · 2026Article
- Age-related changes to brain energetics revealed by PET/MRI imaging.NeuroImage. Clinical · 2026Article
- Reprogramming microglia in sepsis-associated encephalopathy: from pathological dysfunction to therapeutic restoration.Frontiers in immunology · 2026Review
- Dynamic changes in mitochondria support phenotypic flexibility of microglia.Nature communications · 2025Article
- Midbrain extracellular matrix and microglia are associated with cognition in aging mice.Nature communications · 2025Article
- Interplay Between Aging and Glial Cell Dysfunction: Implications for CNS Health.Life (Basel, Switzerland) · 2025Review
- Identification and Characterization of a Translational Mouse Model for Blood-Brain Barrier Leakage in Cerebral Small Vessel Disease.International journal of molecular sciences · 2025Article
- FKBP51 inhibition ameliorates neurodegeneration and motor dysfunction in the neuromelanin-SNCA mouse model of Parkinson's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Astrocytes in aging.Neuron · 2025Review
- Adolescent Alcohol and the Spectrum of Cognitive Dysfunction in Aging.Advances in experimental medicine and biology · 2025Review
- TBC1D15 Inhibits Autophagy of Microglia through Maintaining the Damaged Swelling Lysosome in Alzheimer's Disease.Aging and disease · 2024Article
- Navigating the Neuroimmunomodulation Frontier: Pioneering Approaches and Promising Horizons-A Comprehensive Review.International journal of molecular sciences · 2024Review
- Microglial responses to inflammatory challenge in adult rats altered by developmental exposure to polychlorinated biphenyls in a sex-specific manner.Neurotoxicology · 2024Article
- Epigenetic heterogeneity shapes the transcriptional landscape of regional microglia.bioRxiv : the preprint server for biology · 2024Article
- Microglia in brain aging: An overview of recent basic science and clinical research developments.Journal of biomedical research · 2024Article
- Dopamine enhances recovery after traumatic brain injury through ubiquitylation and autophagic degradation of RIPK1.Cell communication and signaling : CCS · 2024Article
- The proteomic landscape of microglia in health and disease.Frontiers in cellular neuroscience · 2024Review
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
During aging, microglia produce inflammatory factors, show reduced tissue surveillance, altered interactions with synapses, and prolonged responses to CNS insults, positioning these cells to have profound impact on the function of nearby neurons. We and others recently showed that microglial attributes differ significantly across brain regions in young adult mice. However, the degree to which microglial properties vary during aging is largely unexplored. Here, we analyze and manipulate microglial aging within the basal ganglia, brain circuits that exhibit prominent regional microglial heterogeneity and where neurons are vulnerable to functional decline and neurodegenerative disease. In male and female mice, we demonstrate that VTA and SNc microglia exhibit unique and premature responses to aging, compared with cortex and NAc microglia. This is associated with localized VTA/SNc neuroinflammation that may compromise synaptic function as early as middle age. Surprisingly, systemic inflammation, local neuron death, and astrocyte aging do not appear to underlie these early aging responses of VTA and SNc microglia. Instead, we found that microglial lysosome status was tightly linked to early aging of VTA microglia. Microglial ablation/repopulation normalized VTA microglial lysosome swelling and suppressed increases in VTA microglial density during aging. In contrast, CX3CR1 receptor KO exacerbated VTA microglial lysosome rearrangements and VTA microglial proliferation during aging. Our findings reveal a previously unappreciated regional variation in onset and magnitude of microglial proliferation and inflammatory factor production during aging and highlight critical links between microglial lysosome status and local microglial responses to aging.
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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.