Neuro-vascular wiring in obese mice

Monday, September 22, 2014 — Poster Session I
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NHLBI	DEVBIO-10

Authors

• T Yamazaki
• W Li
• Y Mukouyama

Abstract

Diabetic neuropathy is a common diabetic complication that leads to a deficient sensory system. How metabolic factors such as high blood glucose in the circulatory system lead to damage to neighboring nerves remains elusive. We have recently established a high-resolution whole-mount imaging protocol for adult ear skins to visualize branching morphogenesis of nerves and blood vessels. Using the whole-mount imaging system, we have examined what happens to neuro-vascular wiring in diet-induced obesity (DIO) mice, which model a severe pathology found in human diabetic neuropathy. We have found a collapse of sensory nerve bundles and depletion of αSMA + vascular smooth muscle cells (VSMCs) in the DIO mice. This surprising result suggests that neuronal damage occurs early in diabetes. We are currently investigating the possibility that chronic inflammation-induced recruitment of macrophages and dendritic cells may trigger the disruption of neuro-vascular wiring. We have found a significant increase and accumulation of CD11b+ inflammatory macrophages in the DIO skin, suggesting that inflammatory macrophages may play a major role in obesity-induced axon degeneration. We attempt to carry out an anti-inflammation treatment and a systemic macrophage/monocyte depletion. These studies will provide insight to understanding pathogenesis of diabetic neuropathy.

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