Marilyn J Duncan

Age-related changes in circadian rhythms 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 sectionssignals. 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. M. Hester, J.A. Hopper, K.M. Franklin (2010) The effects of aging and chronic fluoxetine treatment on circadian rhythms and suprachiasmatic nucleus expression of neuropeptide genes and 5-HT1B receptors. Eur. J. Neurosci. 31:1646-1654 Duncan, M.J., Congleton, M.R. (2010) Neural mechanism mediating circadian phase resetting by activation of 5-HT7 receptors in the dorsal raphe: Role of GABAergic and glutamatergic neurotransmission, Brain Research 1366:110-119. Legan, S.J., X-L. Peng, K.M. Franklin, and M.J. Duncan (2010) Novel wheel running blocks the preovulatory luteinizing hormone (LH) surge as well as advances the hamster circadian pacemaker. J. Biol. Rhythms 25:450-459. Benca, R., M.J. Duncan, E. Frank, C. McClung, R.J. Nelson, and A.Vincentic (2009) Biological rhythms, higher brain function and behavior: Gaps, opportunities and challenges, Brain Research Reviews 62:57-70. Legan, S.J., K.M. Franklin, K.M.,Donoghue, and M.J. Duncan (2009) Phenobarbital blockade of the preovulatory LH surge: Association with phase-advanced circadian clock and altered suprachiasmatic nucleus Period1 gene expression. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296: R1620-1630. PMCID 2689824 Duncan, M.J., A. Bruce-Keller, C. Conner, P.E. Knapp,R. Xu, A. Nath, and K.F. Hauser (2008) Effects of chronic expression of the HIV protein, transactivator of transcription (Tat), on circadian activity rhythms in mice with or without morphine. Am. J. Physiol. Regul. Integr. Comp. Physiol. 295:R1680-1687. PMCID 2584859 Duncan, M.J. (2006-2007) 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. 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:R180-188. Duncan, M.J., and V.A. Davis. (2005) Cyclic AMP mediates circadian phase shifts induced by microinjection of serotonergic drugs in the hamster dorsal raphe nucleus. Brain Research 1058:10-16. 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. Duncan, M.J., K.E. Grear, and M.A. Hoskins (2004) 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. 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., and J.G. Hensler (2002) Aging alters in a region-specific manner serotonin transporter sites and 5–HT1A receptor-G protein interactions in hamster brain. Neuropharmacol. 43:36-44.