ArticlePLoS biology2024
Aberrant activation of hippocampal astrocytes causes neuroinflammation and cognitive decline in mice.
Article in PLoS biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Silibinin Alleviates Cognitive Dysfunction, Biochemical Alterations, and Hippocampal Structural Changes Induced by 5 days of Sleep Deprivation with or Without a Subsequent 24-H Recovery in Rats.Molecular neurobiology · 2026Article
- The multiple scales of astrocytic functional units.Nature neuroscience · 2026Review
- Secondary demyelination after stroke: Glial cell crosstalk.IBRO neuroscience reports · 2026Review
- miR‑16‑5p Protects RGCs Against Retinal Ischemia-Reperfusion Injury by Modulating Astrocyte-Mediated Neuroinflammation Through the Wip1/NF-κB Signaling Axis.Molecular neurobiology · 2026Article
- PTP1B in astrocytes drives pathogen-induced neurodegeneration.Journal of neuroinflammation · 2026Article
- DRP1 induces neuroinflammation via transcriptional regulation of NF-ĸB.Nature communications · 2026Article
- Lipocalin-2 in Intracerebral Hemorrhage: Mechanisms, Biomarker Potential, and Therapeutic Targeting.Neuromolecular medicine · 2026Review
- Lcn2 deficiency leads to long-lasting social impairments independent of maternal immune activation.Journal of neuroinflammation · 2026Article
- Neuroprotective Effects of Desert Milk Exosomes in LPS-Induced Cognitive Decline: Role of Microglial M2 Polarization and AMPK Signaling.Nutrients · 2026Article
- Regulatory mechanisms and research progress of astrocytes in the neuro-endocrine-immune network.Frontiers in human neuroscience · 2026Review
- Effect of regular treadmill exercise on astrocyte proliferation-related proteins in the motor cortex and hippocampus after traumatic brain injury.Journal of exercise rehabilitation · 2025Article
- Mild Cognitive Impairment and Sarcopenia: Effects of Resistance Exercise Training on Neuroinflammation, Cognitive Performance, and Structural Brain Changes.International journal of molecular sciences · 2025Review
- Decreased hippocampal neurite density in late-middle-aged adults following prenatal exposure to higher levels of maternal inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Astrocytes as Active Participants in Memory.Journal of neurochemistry · 2025Review
- Decreased hippocampal neurite density in late middle-aged adults following prenatal exposure to higher levels of maternal inflammation.bioRxiv : the preprint server for biology · 2025Article
- Neuroimmune signaling mediates astrocytic nucleocytoplasmic disruptions and stress granule formation associated with TDP-43 pathology.Neurobiology of disease · 2025Article
- Chronic Chemogenetic Activation of Astrocytes in the Murine Mesopontine Region Leads to Disturbances in Circadian Activity and Movement.International journal of molecular sciences · 2025Article
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- Lipocalin-2 in preoperative cerebrospinal fluid is a biomarker for postoperative delirium after hip fracture surgery in older adults: a prospective cohort study.Frontiers in neurology · 2025Article
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Abstract
Reactive astrocytes are associated with neuroinflammation and cognitive decline in diverse neuropathologies; however, the underlying mechanisms are unclear. We used optogenetic and chemogenetic tools to identify the crucial roles of the hippocampal CA1 astrocytes in cognitive decline. Our results showed that repeated optogenetic stimulation of the hippocampal CA1 astrocytes induced cognitive impairment in mice and decreased synaptic long-term potentiation (LTP), which was accompanied by the appearance of inflammatory astrocytes. Mechanistic studies conducted using knockout animal models and hippocampal neuronal cultures showed that lipocalin-2 (LCN2), derived from reactive astrocytes, mediated neuroinflammation and induced cognitive impairment by decreasing the LTP through the reduction of neuronal NMDA receptors. Sustained chemogenetic stimulation of hippocampal astrocytes provided similar results. Conversely, these phenomena were attenuated by a metabolic inhibitor of astrocytes. Fiber photometry using GCaMP revealed a high level of hippocampal astrocyte activation in the neuroinflammation model. Our findings suggest that reactive astrocytes in the hippocampus are sufficient and required to induce cognitive decline through LCN2 release and synaptic modulation. This abnormal glial-neuron interaction may contribute to the pathogenesis of cognitive disturbances in neuroinflammation-associated brain conditions.
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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.