Our long-term research objective is to understand the molecular mechanisms that initiate circadian gene expression following external stimulation. We will use the pineal gland to study signaling pathways because it has been extensively used to study signaling cascades and so provides an extensive knowledgebase for our studies. Our research proposal has two goals: (1) to understand the mechanisms by which norepinepherine (NE) controls Period1 expression and (2) to investigate the regulation of circadian """"""""Clock"""""""" genes' expressions following external stimulation. First, since NE increases intra-cellular cyclic AMP (cAMP) and cyclic GMP (cGMP) levels, we will investigate the mechanisms by which cAMP and cGMP signaling pathways induce Period 1 mRNA levels. Since Period 1 is thought to be involved in the resetting of circadian rhythms, we will focus on the regulation of Period 1 expression in specific aims I and I1. Secondly, we will investigate whether or not other circadian """"""""Clock"""""""" mRNA levels are induced by NE, cAMP, cGMP, or cAMP and cGMP co-stimulation. Besides its biological importance and interest, the use of pineal gland as a model, has promise for providing information that may be applicable to the prevention of neurodegenerative diseases, such as Alzheimer's disease, since it has been suggested that melatonin may play a role in neuroprotection. In addition, our studies have the pete"""""""" tial to address problems associated with jet lag, circadian-based sleep disorders, some neuropsychiatric illnesses, and shift work.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center--Cooperative Agreements (U54)
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Morehouse School of Medicine
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Pulliam, John V K; Xu, Zhenfeng; Ford, Gregory D et al. (2013) Computational identification of conserved transcription factor binding sites upstream of genes induced in rat brain by transient focal ischemic stroke. Brain Res 1495:76-85
Li, Yonggang; Lein, Pamela J; Liu, Cuimei et al. (2012) Neuregulin-1 is neuroprotective in a rat model of organophosphate-induced delayed neuronal injury. Toxicol Appl Pharmacol 262:194-204
Rodriguez-Mercado, Rafael; Ford, Gregory D; Xu, Zhenfeng et al. (2012) Acute neuronal injury and blood genomic profiles in a nonhuman primate model for ischemic stroke. Comp Med 62:427-38
Mong, Jessica A; Baker, Fiona C; Mahoney, Megan M et al. (2011) Sleep, rhythms, and the endocrine brain: influence of sex and gonadal hormones. J Neurosci 31:16107-16
Guo, Qingmin; Wang, Guangming; Namura, Shobu (2010) Fenofibrate improves cerebral blood flow after middle cerebral artery occlusion in mice. J Cereb Blood Flow Metab 30:70-8
Davidson, Alec J; Castanon-Cervantes, Oscar; Leise, Tanya L et al. (2009) Visualizing jet lag in the mouse suprachiasmatic nucleus and peripheral circadian timing system. Eur J Neurosci 29:171-80
Wang, Guangming; Guo, Qingmin; Hossain, Mohammed et al. (2009) Bone marrow-derived cells are the major source of MMP-9 contributing to blood-brain barrier dysfunction and infarct formation after ischemic stroke in mice. Brain Res 1294:183-92
Paul, Ketema N; Laposky, Aaron D; Turek, Fred W (2009) Reproductive hormone replacement alters sleep in mice. Neurosci Lett 463:239-43
Guo, Qingmin; Wang, Guangming; Liu, Xiaowei et al. (2009) Effects of gemfibrozil on outcome after permanent middle cerebral artery occlusion in mice. Brain Res 1279:121-30
Fukuhara, Chiaki; Tosini, Gianluca (2008) Analysis of daily and circadian gene expression in the rat pineal gland. Neurosci Res 60:192-8

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