William Engeland, PhD
Professor Emeritus, Department of Neuroscience
Professor Emeritus, Department of Neuroscience
Neuroendocrinology of stress
The focus of the laboratory is to delineate neuroendocrine mechanisms for the control of adrenal secretion of glucocorticoids, the major output of the hypothalamic-pituitary-adrenal (HPA) axis. One goal is to define the role of adrenal innervation on the control of glucocorticoid secretion. The secretion of the adrenal cortex is dependent on the pituitary hormone, ACTH. Our work has shown that autonomic neural activity contributes to circadian and stress-induced corticosteroid secretion by modulating steroidogenic responses to ACTH, but the central and peripheral neural pathways involved have not been delineated.
To characterize the central neural substrate for circadian changes in glucocorticoids, a combination of a physiological and neuroanatomical methods are employed; plasma ACTH, vasopressin and adrenal steroids are measured and double-label immunohistochemistry and retrograde labeling are used to define the phenotype of neurons activated as a function of time of day. The hypothesis to be tested is that neurons in the paraventricular nucleus (PVN) of the hypothalamus receive input from the suprachiasmatic nucleus (SCN) and project to the spinal cord to provide inhibitory and excitatory input to the adrenal cortex that drives the circadian rhythm.
Other studies are determining the central and peripheral mechanisms that control rapid decreases in glucocorticoids. By active removal of a stressor, rehydration after water restriction or feeding after food restriction are viewed as unique models for assessing processes invoked to reduce stress as reflected by decreases in HPA activity. Using Fos immunohistochemistry coupled with phenotypic labeling, our studies have identified a unique pattern of neural activity in the PVN induced by drinking after repeated water restriction that is not observed after a single episode of water deprivation. Experiments will incorporate microdialysis with CE-LIF detection to determine neurotransmitters released in the PVN that mediate changes in neural and endocrine responses. The goal of this work is to identify central neural circuits controlling HPA activity that could be mobilized to reduce the deleterious effects of stress.
Razzoli, M, Lindsay, A, Law, ML, Chamberlain, CM, Southern, WM, Berg, M, Osborn, J, Engeland, WC, Metzger, JM, Ervasti, JM & Bartolomucci 2020, ‘A Social stress is lethal in the mdx model of Duchenne muscular dystrophy’ EBioMedicine, p. 102700. https://doi.org/10.1016/j.ebiom.2020.102700
Engeland, WC, Massman, L, Miller, L, Leng, S, Pignatti, E, Pantano, L, Carlone, DL, Kofuji, P & Breault, DT 2019, ‘Sex Differences in Adrenal Bmal1 Deletion-Induced Augmentation of Glucocorticoid Responses to Stress and ACTH in Mice’ Endocrinology, vol. 160, no. 10, pp. 2215-2229. https://doi.org/10.1210/en.2019-00357
Engeland, WC, Massman, L, Mishra, S, Yoder, JM, Leng, S, Pignatti, E, Piper, ME, Carlone, DL, Breault, DT & Kofuji, P 2018, ‘The Adrenal Clock Prevents Aberrant Light-Induced Alterations in Circadian Glucocorticoid Rhythms’ Endocrinology, vol. 159, no. 12, pp. 3950-3964. https://doi.org/10.1210/en.2018-00769
Kofuji, P, Mure, LS, Massman, LJ, Purrier, N, Panda, S & Engeland, WC 2016, ‘Intrinsically Photosensitive Retinal Ganglion Cells (ipRGCs) Are Necessary for Light Entrainment of Peripheral Clocks’ PLoS One, vol. 11, no. 12, pp. e0168651. https://doi.org/10.1371/journal.pone.0168651
Engeland, WC, Yoder, JM, Karsten, CA & Kofuji, P 2016, ‘Phase-Dependent Shifting of the Adrenal Clock by Acute Stress-Induced ACTH’ Front Endocrinol (Lausanne), vol. 7, pp. 81. https://doi.org/10.3389/fendo.2016.00081
Razzoli, M, McCallum, J, Gurney, A, Engeland, WC & Bartolomucci, A 2015, ‘Chronic stress aggravates glucose intolerance in leptin receptor-deficient (db/db) mice’ Genes Nutr, vol. 10, no. 3, pp. 458. https://doi.org/10.1007/s12263-015-0458-2
Foss, JD, Wainford, RD, Engeland, WC, Fink, GD & Osborn, JW 2015, ‘A novel method of selective ablation of afferent renal nerves by periaxonal application of capsaicin’ Am J Physiol Regul Integr Comp Physiol, vol. 308, no. 2, pp. R112-22. https://doi.org/10.1152/ajpregu.00427.2014
Raff, H, Gehrand, A, Bruder, ED, Hoffman, MJ, Engeland, WC & Moreno, C 2015, ‘Renin knockout rat: control of adrenal aldosterone and corticosterone synthesis in vitro and adrenal gene expression’ Am J Physiol Regul Integr Comp Physiol, vol. 308, no.1, pp. R73-7. https://doi.org/10.1152/ajpregu.00440.2014
Purrier, N, Engeland, WC & Kofuji, P 2014, ‘Mice deficient of glutamatergic signaling from intrinsically photosensitive retinal ganglion cells exhibit abnormal circadian photoentrainment’ PLoS One, vol. 9, no. 10, pp. e111449. https://doi.org/10.1371/journal.pone.0111449
Razzoli, M, Karsten, C, Yoder, JM, Bartolomucci, A & Engeland, WC 2014, ‘Chronic subordination stress phase advances adrenal and anterior pituitary clock gene rhythms’ Am J Physiol Regul Integr Comp Physiol, vol. 307, no. 2, pp. R198-205. https://doi.org/10.1152/ajpregu.00101.2014
NSCI 6110: Neuroscience for Dental Students (Spring semester)