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Updated: Feb 16, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglia modulation through external vagus nerve stimulation in a murine model of Alzheimer's disease
Robert Kaczmarczyk1, Dario Tejera1, Bruce J Simon2
1Department of Neurodegenerative Disease and Gerontopsychiatry, University of Bonn, Bonn, Germany.
Abstract:
Chronically activated microglia contribute to the development of neurodegenerative diseases such as Alzheimer's disease (AD) by the release of pro-inflammatory mediators that compromise neuronal function and structure. Modulating microglia functions could be instrumental to interfere with disease pathogenesis. Previous studies have shown anti-inflammatory effects of acetylcholine (ACh) or norepinephrine (NE), which mainly activates the β-receptors on microglial cells. Non-invasive vagus nerve stimulation (nVNS) is used in treatment of drug-resistant depression, which is a risk factor for developing AD. The vagus nerve projects to the brainstem's locus coeruleus from which noradrenergic fibers reach to the Nucleus Basalis of Meynert (NBM) and widely throughout the brain. Pilot studies showed first signs of cognitive-enhancing effects of nVNS in AD patients. In this study, the effects of nVNS on mouse microglia cell morphology were analyzed over a period of 280 min by 2-photon laser scanning in vivo microscopy. Total branch length, average branch order and number of branches, which are commonly used indicators for the microglial activation state were determined and compared between young and old wild-type and amyloid precursor protein/presenilin-1 (APP/PS1) transgenic mice. Overall, these experiments show strong morphological changes in microglia, from a neurodestructive to a neuroprotective phenotype, following a brief nVNS in aged animals, especially in APP/PS1 animals, whereas microglia from young animals were morphologically unaffected.
Insights
Non-invasive vagus nerve stimulation (nVNS) shifts microglia from a harmful to a protective state in aged mice, particularly those with Alzheimer
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Chronically activated microglia exacerbate neurodegenerative diseases like Alzheimer's disease (AD) through pro-inflammatory signaling.
- Modulating microglial function offers a therapeutic strategy for AD pathogenesis.
- Norepinephrine (NE) and acetylcholine (ACh) exhibit anti-inflammatory effects on microglia, while non-invasive vagus nerve stimulation (nVNS) influences NE pathways.
Purpose of the Study:
- To investigate the impact of nVNS on microglial morphology in young and aged wild-type and AD model (APP/PS1) mice.
- To determine if nVNS can alter microglial activation states towards a neuroprotective phenotype.
Main Methods:
- In vivo 2-photon laser scanning microscopy was used to analyze microglial morphology over 280 minutes.
- Key indicators of microglial activation, including total branch length, average branch order, and number of branches, were quantified.
- Comparisons were made between young and aged wild-type mice and young and aged APP/PS1 transgenic mice.
Main Results:
- Non-invasive vagus nerve stimulation induced significant morphological changes in microglia of aged mice.
- These changes indicate a shift from a neurodestructive to a neuroprotective microglial phenotype, particularly evident in aged APP/PS1 mice.
- Microglia in young animals did not exhibit significant morphological alterations following nVNS.
Conclusions:
- Non-invasive vagus nerve stimulation demonstrates potential in modulating microglial phenotype towards a neuroprotective state in aged and Alzheimer's disease models.
- These findings suggest nVNS as a potential therapeutic approach for neurodegenerative conditions characterized by microglial dysfunction.
- Further research is warranted to explore the long-term effects and underlying mechanisms of nVNS on neuroinflammation.
