Dr. Veasey’s laboratory focuses on metabolic injury to wake-active neurons and neural injury incurred by hypoxia/reoxygenation events of obstructive sleep apnea. The lab uses a diverse array of molecular and imaging techniques to answer clinically relevant questions in Sleep Medicine: How are wake neurons injured with aging and other metabolic challenges? How does sleep apnea injure neurons? The overreaching goal is towards developing therapies to prevent neural injury.
Wake-active neurons in the brain are essential for optimal wakefulness and cognitive performance.
Although there are many groups of these neurons, each playing unique roles in wake responses, the catecholaminergic wake neurons in the locus coeruleus and dorsal midbrain are particularly sensitive to diverse injuries, including aging and neurodegenerative processes. We have recently identified SIRT1 as a key regulator of wake-active neuron function and integritys, one that is lost with aging. A key focus for the lab now is to identify why this is lost and why wake neurons rely so heavily on this protectant.
The second focus for the lab is neural injury in sleep apnea. Dr. Veasey's lab identified the specific wake active neuronal populations injured by hypoxia/reoxygenation, the two catecholaminergic groups the noradrenergic locus coeruleus and dopmainergic periacqueductal grey wake neurons. By comparing phenotypes and responses in these vulnerable to resistant wake neuronal populations, her group identified NADPH oxidase as a major contributor to the oxidative injury. Dr. Veasey is now comparing and contrasting these responses with other groups of neurons known to be injured in obstructive sleep apnea. The goal is to find major mechanisms of injury in hippocampal, hypothalamic and cortical neurons and then begin translational studies to identify the optimal overall pharmacotherapeutic approach to prevent or minimize neural injury in sleep apnea.
Beier UH, Angelin A, Akimova T, Wang L, Liu Y, Xiao H, Koike MA, Hancock SA, Bhatti TR, Han R, Jiao J, Veasey SC, Sims CA, Baur JA, Wallace DC, Hancock WW.: Essential role of mitochondrial energy metabolism in Foxp3+ T-regulatory cell function and allograft survival. FASEB J. in press, 2015.
Yan Zhu, Polina Fenik, Guan Xia Zhan and Sigrid Veasey: Degeneration in Arousal Neurons in Chronic Sleep Disruption Modeling Sleep Apnea. Frontiers in Neurology in press, 2015.
Zhang, J., Zhu, Y., Zhan, G., Fenik, P., Panossian, L., Wang, M.M., Reid, S., Lai, D., Davis, J.G., Baur, J.A., Veasey, S.: Extended wakefulness: compromised metabolics in and degeneration of locus ceruleus neurons
J Neurosci 34(12): 4418-4431, March 2014
Zhang, J., Peng, H., Veasey, S.C., Ma, J., Wang, G.F., Wang, K.W.: Blockade of Na+/H+ exchanger type 3 causes intracellular acidification and hyperexcitability via inhibition of pH-sensitive K+ channels in chemosensitive respiratory neurons of the dorsal vagal nucleus in rats. Neuroscience Bulletin 30(1): 43-52, Feb 2014.
Li, Y., Panossian, L.A., Zhang, J., Zhu, Y., Zhan, G., Chou, Y.T., Fenik, P., Bhatnagar, S., Piel, D.A., Beck, S.G., Veasey, S.: Effects of chronic sleep fragmentation on wake-active neurons and the hypercapnic arousal response. Sleep 36(10): 1471-1481, October 2013.
Chou, Y., Zhan, G., Zhu, Y., Fenik, P., Panossian, L., Li, Y., Zhang, J., Veasey, S.: C/EBP homologous binding protein (CHOP) underlies neural injury in sleep apnea model
Sleep 36(4): 481-492, Apr 2013.
Veasey, S., White, D.P.: Obstructive sleep apnea pharmacotherapy: one step closer. American Journal of Respiratory and Critical Care Medicine 187(3): 226-227, Feb 2013.
Moore, J.T., Chen, J., Han, B., Meng, Q.C., Veasey, S.C., Beck, S.G., Kelz, M.B.: Direct activation of sleep-promoting VLPO neurons by volatile anesthetics contributes to anesthetic hypnosis. Current Biology 22(21): 2008-2016, Nov 2012.
Veasey, S.C.: Piecing together phenotypes of brain injury and dysfunction in obstructive sleep apnea. Frontiers in Neurology 3: 139, Oct 2012.
Li, Y., Veasey, S.C.: Neurobiology and neuropathophysiology of obstructive sleep apnea. Neuromolecular Medicine 14(3): 168-179, Sep 2012.
back to top
Last updated: 05/19/2015
The Trustees of the University of Pennsylvania