Title: Chronic intermittent hypoxia induces remodeling of catecholaminergic axon innervation in the mouse atria (association with migraine)
Presenter: Ariege Bizanti, PhD student, University of Central Florida, US
Methodology, findings and conclusions of the research
We exposed mice to either room air condition or chronic intermittent hypoxia that mimics the sleep apnea condition in humans. Then, the whole left and right atria were prepared and immunolabeled with tyrosine hydroxylase (a sympathetic marker). Chronic intermittent hypoxia-induced structural remodeling was subsequently determined by imaging, nerve tracing and reconstruction of catecholaminergic (sympathetic) innervation of the heart. Our results showed that hypoxia induced remodeling of sympathetic innervation by increasing the density of nerve innervation (especially in the sinoatrial node), increased the complexity of nerve bundles and terminals, and increased the tortuosity and innervation of different cardiac targets. Our findings suggest that sympathetic innervation may further exacerbate the effects of enhanced hypoxia-induced central sympathetic drive to the heart.
Implications of the research for understanding migraine and/or its comorbidities
Chronic intermittent hypoxia is a hallmark of sleep apnea, which is associated with induced migraine attacks. Hypoxia is known to induce migraine-like attacks for several reasons. One reason is the sudden and rapid increase in pressure inside the head in response to hypoxia, which leads to pounding/throbbing headache. Another reason is that hypoxia is involved in the release of nitric oxide and calcitonin gene-related peptide, disruption of the blood-brain barrier, and neuro-inflammation, which are underlying pathophysiological mechanisms of migraine. Our technique of studying the hypoxia-induced remodeling of autonomic innervation could give insight into the effects of migraine on changes in the neural network, and could potentially guide the development of more specific therapeutic targets that could reverse the autonomic innervation remodeling.