[en] 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.
Disciplines :
Neurology
Author, co-author :
Kaczmarczyk, Robert; Department of Neurodegenerative Disease and Gerontopsychiatry, University of Bonn, Bonn, Germany
Tejera, Dario; Department of Neurodegenerative Disease and Gerontopsychiatry, University of Bonn, Bonn, Germany
Simon, Bruce J; electroCore LLC, Basking Ridge, New Jersey, USA
HENEKA, Michael ; Department of Neurodegenerative Disease and Gerontopsychiatry, University of Bonn, Bonn, Germany
External co-authors :
yes
Language :
English
Title :
Microglia modulation through external vagus nerve stimulation in a murine model of Alzheimer's disease.
The authors thank Professor Emeritus Russell V. Lenth from the Department of Statistics and Actuarial Science of the University of Iowa for the refinement of the lsmeans package according to our needs. This study was supported by the Deutsche Forschungsgemeinschaft (SFB 1089). Michael Heneka is an editor for the Journal of Neurochemistry. The other authors declare no conflict of interest. All experiments were conducted in compliance with the ARRIVE guidelines.The authors thank Professor Emeritus Russell V. Lenth from the Department of Statistics and Actuarial Science of the University of Iowa for the refinement of the lsmeans package according to our needs. This study was supported by the Deutsche Forschungsgemeinschaft (SFB 1089). Michael Heneka is an editor for the Journal of Neurochemistry. The other authors declare no conflict of interest.
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