Microglia modulation through external vagus nerve stimulation in a murine model of Alzheimer's disease.
Robert KaczmarczykDario TejeraBruce J SimonMichael T HenekaPublished in: Journal of neurochemistry (2017)
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.
Keyphrases
- inflammatory response
- neuropathic pain
- drug resistant
- lipopolysaccharide induced
- lps induced
- spinal cord
- end stage renal disease
- multidrug resistant
- wild type
- anti inflammatory
- high resolution
- induced apoptosis
- cognitive decline
- spinal cord injury
- ejection fraction
- chronic kidney disease
- randomized controlled trial
- cerebral ischemia
- signaling pathway
- white matter
- small molecule
- case control
- peritoneal dialysis
- multiple sclerosis
- prognostic factors
- depressive symptoms
- living cells
- middle aged
- physical activity
- mild cognitive impairment
- quality improvement
- cystic fibrosis
- cell death
- clinical trial
- brain injury
- protein protein
- mass spectrometry
- sleep quality
- resting state
- mesenchymal stem cells
- binding protein
- fluorescent probe
- bone marrow