Microglia modulation through external vagus nerve stimulation in a murine model of Alzheimer's disease

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 disea...

Full description

Saved in:
Bibliographic Details
Published in:Journal of neurochemistry 2018-07, Vol.146 (1), p.76-85
Main Authors: Kaczmarczyk, Robert, Tejera, Dario, Simon, Bruce J., Heneka, Michael T.
Format: Article
Language:English
Subjects:
2‐photon microscopy
Acetylcholine
Alzheimer's disease
Amyloid precursor protein
Animal models
Animals
APP/PS1 mouse
Brain
Brain stem
Cell morphology
Cognitive ability
Cytology
Fibers
Inflammation
Locus coeruleus
Mental depression
Microglia
microglia morphology
Microglial cells
Microscopy
Morphology
Neurodegenerative diseases
Neurological diseases
Neuroprotection
Norepinephrine
Nucleus basalis
Pathogenesis
Phenotypes
Presenilin 1
Proteins
Receptors
Risk factors
Rodents
Stimulation
Structure-function relationships
Transgenic mice
Vagus nerve
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Microglia activation plays an important role in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease and in acute brain trauma, including stroke and traumatic brain injury. Non‐invasive vagus nerve stimulation (nVNS) is able to revert the neuroinflammatory phenotype of microglia in a mouse model of AD. nVNS is thought to exert this effect by the release of norepinephrine and acetylcholine from the locus coeruleus and nucleus basalis of Meynert, respectively. nVNS may therefore provide a novel treatment paradigm for neurodegenerative diseases by inducing the neuroprotective action of microglia and suppressing the detrimental release of proinflammatory mediators.
ISSN:0022-3042
1471-4159
DOI:10.1111/jnc.14284