ArticleActa neuropathologica communications2021
Loss of cholinergic innervation differentially affects eNOS-mediated blood flow, drainage of Aβ and cerebral amyloid angiopathy in the cortex and hippocampus of adult mice.
Article in Acta neuropathologica communications, 2021. 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, 34 citations in OpenAlex.
- From Dysbiosis to Blood-Brain Barrier Disruption: The Metabolite-Mediated Gut-Brain Axis in Alzheimer's Disease.Molecular neurobiology · 2026Review
- Reduction in hippocampal cholinergic neurostimulating peptide enhances memory impairment in AppAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Electroacupuncture alleviates cognitive impairment in mice with vascular dementia by regulating the cholinergic vasodilation system.Frontiers in aging neuroscience · 2026Article
- Cholinergic basal forebrain neurons regulate vascular dynamics and cerebrospinal fluid flux.Nature communications · 2025Article
- Stroke Exacerbates Respiratory Disorder and Cognition Impairment in Mice with Cerebral Amyloid Angiopathy.Aging and disease · 2025Article
- The microcirculation, the blood-brain barrier, and the neurovascular unit in health and Alzheimer disease: The aberrant pericyte is a central player.Pharmacological reviews · 2025Review
- Cerebral Small Vessel Disease: Therapeutic Approaches Targeting Neuroinflammation, Oxidative Stress, and Endothelial Dysfunction.Current issues in molecular biology · 2025Review
- Visual hallucinations in Parkinson's disease: spotlight on central cholinergic dysfunction.Brain : a journal of neurology · 2025Review
- Evolution of Alzheimer's Disease Therapeutics: From Conventional Drugs to Medicinal Plants, Immunotherapy, Microbiotherapy and Nanotherapy.Pharmaceutics · 2025Review
- White matter hyperintensities and cholinergic degeneration as Lewy body disease.Annals of clinical and translational neurology · 2025Article
- Enhanced prefrontal nicotinic signaling as evidence of active compensation in Alzheimer's disease models.Translational neurodegeneration · 2024Article
- Protein arginine methyltransferase 4 modulates nitric oxide synthase uncoupling and cerebral blood flow in Alzheimer's disease.Journal of cellular physiology · 2024Article
- Chronic inflammation with microglia senescence at basal forebrain: impact on cholinergic deficit in Alzheimer's brain haemodynamics.Brain communications · 2024Article
- Approaches for Increasing Cerebral Efflux of Amyloid-β in Experimental Systems.Journal of Alzheimer's disease : JAD · 2024Review
- Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Intranasal nerve growth factor for prevention and recovery of the outcomes of traumatic brain injury.Neural regeneration research · 2023Review
- The lymphatic drainage systems in the brain: a novel target for ischemic stroke?Neural regeneration research · 2023Review
- Involvement of an Aberrant Vascular System in Neurodevelopmental, Neuropsychiatric, and Neuro-Degenerative Diseases.Life (Basel, Switzerland) · 2023Review
- Neurovascular coupling mechanisms in health and neurovascular uncoupling in Alzheimer's disease.Brain : a journal of neurology · 2022Article
- Deciphering therapeutic options for neurodegenerative diseases: insights from SIRT1.Journal of molecular medicine (Berlin, Germany) · 2022Review
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular dysregulation and cholinergic basal forebrain degeneration are both early pathological events in the development of Alzheimer's disease (AD). Acetylcholine contributes to localised arterial dilatation and increased cerebral blood flow (CBF) during neurovascular coupling via activation of endothelial nitric oxide synthase (eNOS). Decreased vascular reactivity is suggested to contribute to impaired clearance of β-amyloid (Aβ) along intramural periarterial drainage (IPAD) pathways of the brain, leading to the development of cerebral amyloid angiopathy (CAA). However, the possible relationship between loss of cholinergic innervation, impaired vasoreactivity and reduced clearance of Aβ from the brain has not been previously investigated. In the present study, intracerebroventricular administration of mu-saporin resulted in significant death of cholinergic neurons and fibres in the medial septum, cortex and hippocampus of C57BL/6 mice. Arterial spin labelling MRI revealed a loss of CBF response to stimulation of eNOS by the Rho-kinase inhibitor fasudil hydrochloride in the cortex of denervated mice. By contrast, the hippocampus remained responsive to drug treatment, in association with altered eNOS expression. Fasudil hydrochloride significantly increased IPAD in the hippocampus of both control and saporin-treated mice, while increased clearance from the cortex was only observed in control animals. Administration of mu-saporin in the TetOAPPSweInd mouse model of AD was associated with a significant and selective increase in Aβ40-positive CAA. These findings support the importance of the interrelationship between cholinergic innervation and vascular function in the aetiology and/or progression of CAA and suggest that combined eNOS/cholinergic therapies may improve the efficiency of Aβ removal from the brain and reduce its deposition as CAA.
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