ArticleJournal of neuroinflammation2023
Chronic neuroinflammation during aging leads to cholinergic neurodegeneration in the mouse medial septum.
Article in Journal of neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- A lifespan staging model of basal forebrain cholinergic vulnerability.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Synaptic aging and neurodegeneration: the role of synaptic vesicle dynamics and neurotransmitter imbalance.Biogerontology · 2026Review
- Optimized detection of caspase-6 activation in a murine inflammation model to inform neurodegenerative disease therapies.PloS one · 2026Article
- Astrocytic KFrontiers in aging neuroscience · 2026Review
- Traumatic brain injury exacerbates alcohol consumption and neuroinflammation with decline in cognition and cholinergic activity.Translational psychiatry · 2025Article
- The medial septum-hippocampus-lateral septum circuitry in spatial memory: linking healthy function to early Alzheimer's disease and translational opportunities.Translational neurodegeneration · 2025Review
- Orexin/Hypocretin Modulates Neuroinflammatory Response to LPS in a Sex and Brain-Region Specific Manner in Young Rats.Journal of neurochemistry · 2025Article
- Potassium homeostasis during disease progression of Alzheimer's disease.The Journal of physiology · 2025Article
- The Hallmarks of Ageing in Microglia.Cellular and molecular neurobiology · 2025Review
- Stress-Induced Sleep Dysregulation: The Roles of Astrocytes and Microglia in Neurodegenerative and Psychiatric Disorders.Biomedicines · 2025Review
- Neural ageing and synaptic plasticity: prioritizing brain health in healthy longevity.Frontiers in aging neuroscience · 2024Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLow-grade, chronic inflammation in the central nervous system characterized by glial reactivity is one of the major hallmarks for aging-related neurodegenerative diseases like Alzheimer's disease (AD). The basal forebrain cholinergic neurons (BFCN) provide the primary source of cholinergic innervation of the human cerebral cortex and may be differentially vulnerable in various neurodegenerative diseases. However, the impact of chronic neuroinflammation on the cholinergic function is still unclear.
methodsTo gain further insight into age-related cholinergic decline, we investigated the cumulative effects of aging and chronic neuroinflammation on the structure and function of the septal cholinergic neurons in transgenic mice expressing interleukin-6 under the GFAP promoter (GFAP-IL6), which maintains a constant level of gliosis. Immunohistochemistry combined with unbiased stereology, single cell 3D morphology analysis and in vitro whole cell patch-clamp measurements were used to validate the structural and functional changes of BFCN and their microglial environment in the medial septum.
resultsStereological estimation of MS microglia number displayed significant increase across all three age groups, while a significant decrease in cholinergic cell number in the adult and aged groups in GFAP-IL6 mice compared to control. Moreover, we observed age-dependent alterations in the electrophysiological properties of cholinergic neurons and an increased excitability profile in the adult GFAP-IL6 group due to chronic neuroinflammation. These results complimented the significant decrease in hippocampal pyramidal spine density seen with aging and neuroinflammation.
conclusionsWe provide evidence of the significant impact of both aging and chronic glial activation on the cholinergic and microglial numbers and morphology in the MS, and alterations in the passive and active electrophysiological membrane properties of septal cholinergic neurons, resulting in cholinergic dysfunction, as seen in AD. Our results indicate that aging combined with gliosis is sufficient to cause cholinergic disruptions in the brain, as seen in dementias.
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