MARILYN J. DUNCAN, Ph.D.

MARILYN J. DUNCAN, Ph.D.
Worcester Foundation for Experimental Biology,
Consortium Program in the Biomedical Sciences (degree
granted through Worcester Polytechnic Institute, 1984)
Postdoctoral training at Massachusetts General Hospital and Northwestern University Medical School
Professor of Anatomy & Neurobiology

Our current studies are directed towards elucidating how aging disrupts biological rhythms. Age-related disintegration of circadian rhythms, especially sleep-wake cycles, lowers resistance to disease and impairs memory and cognitive function. This disintegration results from functional losses in the circadian pacemaker located in the hypothalamic suprachiasmatic nuclei (SCN). The expression of circadian rhythms depends upon the pacemaker’s ability to integrate endogenous and exogenous time Brain sections

signals. During aging, the circadian pacemaker loses its ability to respond to serotonin, one of the neurotransmitters which normally communicates time signals. In order to elucidate the pre- and post-synaptic mechanisms causing age-related desensitization to serotonin, we are studying synaptic release of serotonin, serotonin receptors, the serotonin transporter, as well as the interaction of serotonin with neuropeptides. These studies utilize a variety of neurochemical and behavioral techniques, including receptor autoradiography, computerized image analysis, in situ hybridization, animal surgery, and monitoring of locomotor activity rhythms. This research will provide a rational basis for novel treatments of sleep disorders in the elderly population, as well as in shift-workers and jet travelers.

Duncan, M.J., J. Short and D.L. Wheeler. A comparison of the effects of aging on 5-HT7 and 5-HT1A receptors in discrete regions of the circadian timing system in hamsters. Brain Research, 829: 39-45, 1999.

Duncan, M.J., and D.L. Wheeler. Aging and photoperiod regulate glutamic acid decarboxylase 67messenger RNA expression. Molecular Brain Research, 71:325-331.

Duncan, M.J., C.J. Crafton, and D.L. Wheeler. Aging regulates 5-HT1B receptors and serotonin reuptake sites in the SCN. Brain Research 856: 213-219, 2000.

Duncan, M.J., L. Jennes, J.B. Jefferson, and M.S. Brownfield. Localization of serotonin5A receptors in discrete regions of the circadian timing system in hamsters in the Syrian hamster. Brain Research 869: 178-185, 2000.

Duncan, M.J. and A.W. Deveraux The effect of aging on circadian rhythm responses to dark pulses. Am. J. Physiol. Regul. Integr. Comp Physiol.279:R586-90, 2000.

Duncan, M.J., S.A. Hill, J. M. Herron Aging selectively suppresses VIP messenger RNA expression in the suprachiasmatic nucleus. Molecular Brain Research, 87:196-203, 2001.

Duncan, M.J. and Hensler, J.G. Aging alters in a region-specific manner serotonin transporter sites and 5 HT1A receptor G protein interactions in hamster brain. Neuropharmacology 43: 36-44, 2002.

Krajnak,K., K.L. Rosewell, M.J. Duncan, and P.M. Wise (2003) Aging, estradiol and time of day differentially affect serotonin transporter binding in the central nervous system of female rats. Brain Research 990:87-94.

Duncan, M.J., K.E. Grear, and M.A. Hoskins. Aging and SB-269970-A, a selective 5-HT7 receptor antagonist, attenuate circadian phase shifts induced by microinjections of serotonergic drugs in the hamster dorsal raphe nucleus. Brain Research 1008:40-48.

Duncan, M.J., K. M. Franklin, V.A. Davis, G.H. Grossman, M.E. Knoch, and J.D. Glass. (2005) Short-term constant light potentiation of large-magnitude circadian phase shifts induced by 8-OH-DPAT: Effects on serotonin receptors and gene expression in the hamster suprachiasmatic nucleus. Eur. J. Neurosci. 22:2306-2314.

Knoch, M.E., D. Siegel, M.J. Duncan, and J. D. Glass (2006) Serotonergic mediation of constant light-potentiated nonphotic phase-shifting of the circadian locomotor activity rhythm in Syrian hamsters. Am. J. Physiol. Regul. Integr. Comp Physiol, 291:180-188.

Duncan, M.J. (2006-07) Aging of the mammalian circadian timing system: Changes in the central pacemaker and its regulation by photic and nonphotic signals. Neuroembryology and Aging 4:85-101.

Duncan, M.J. and K. M. Franklin (2007) 5-HT7 receptor mRNA expression in hamster brain: Effect of aging and association with calbindin-D28K mRNA expression. Brain Research 1143:70-77.