Printer Friendly

Associate Professor Department of Physiology

Phone: (252) 744-1905
Fax: (252) 744-3460
E-mail: deanj@ecu.edu

Mailing Address:
Brody School of Medicine, 6N-61
600 Moye Blvd.
Greenville, NC 27834

Circadian rhythms under healthy and diseased conditions

Why do most heart attacks strike before dawn, while asthmatic attacks occur after sunset? The answer to these questions lies in understanding the function of the biological clock in our brain.

The human body is not only structured in space, but also in time. In addition to the overt 24-hour sleep-wake cycle, virtually every bodily function has been shown to exhibit a circadian rhythm in healthy individuals. At a physiological level, body temperature, heart rate, and blood pressure are highest in the afternoon, yet hearing and pain sensitivity are more acute in the evening. Some hormones, such as cortisol and testosterone, are highest in the morning when a person arises, whereas others, such as gastrin, insulin, and renin, are highest in the afternoon or early evening, and yet others, such as melatonin, prolactin, and growth hormone, reach their peak during sleep. Thus, circadian rhythms are part of normal physiology.

Under pathological conditions, some of these bodily rhythms are affected. The amplitude of some circadian rhythms may either be increased or decreased, or the ratio among different variables may be altered. For example, healthy individuals have a robust circadian oscillation of circulating lymphocytes with the peak at night, but this circadian rhythm is diminished in HIV-infected patients. Allergic reactions, such as asthma, hay fever, and hives, usually worsen at night, during sleep, or near wakening. Morbidity and mortality from cardiovascular diseases are more prevalent in the morning hours when the incidence of angina, ischemia, and myocardial infarction is highest.

Circadian rhythms are not passive reflections of the environmental daily light-dark cycle, but instead depend upon an underlying endogenous clock. Situated in the base of the hypothalamus, the suprachiasmatic nucleus (SCN) is the endogenous circadian clock that controls the inner timing of our body. The SCN synchronizes our internal body functions with the environmental daily light-dark cycle and coordinates the activities of the cognitive, autonomic, endocrine, and immune systems.

We study the function of the circadian clock under physiological and pathological conditions using multidisciplinary approaches, including animal behavior, cell and molecular biology, electrophysiology, and genetic techniques.

1.            J. M. Ding, D. Chen, E. T. Weber, L. E. Faiman, M. A. Rea, and M. U. Gillette., Resetting the SCN biological clock: Mediation of Nocturnal Circadian Shifts by Glutamate and NO.  Science. 266 (1994) 1713-1717.

2.            C. Liu, J. M. Ding, L. E. Faiman, and M. U. Gillette.  Coupling of muscarinic cholinergic receptors and cGMP in the nocturnal regulation of the suprachiasmatic circadian clock. Journal of Neuroscience. 17 (1997) 659-666.

3.            J. M. Ding, L. E. Faiman, W. J. Hurst, L. R. Kuriashkina, and M. U. Gillette.  Resetting the biological clock: Mediation of nocturnal CREB phosphorylation through light, glutamate and nitric oxide. Journal of Neuroscience. 17 (1997) 667-675.

4.            J. Hannibal, J. M. Ding, D. Chen, J. Fahrenkrug, P. J. Larsen, M. U. Gillette, and J. D. Mikkelsen.  Pituitary adenylate cyclase activating peptide (PACAP) in the retinohypothalamic tract: A daytime regulator of the biological clock. Journal of Neuroscience. 17 (1997) 2637-2644.

5.            J. M. Ding, G. F. Buchanan, S. A. Tischkau, D. Chen, L. R. Kuriashkina, L. E. Faiman, J. Alster, P. S. McPherson, K. P. Campbell, and M. U. Gillette.  A neuronal ryanodine receptor mediates light-induced phase delays of the circadian rhythm.   Nature. 394 (1998), 381-384.

6.            D. Chen, G. F. Buchanan, J. M. Ding, J. Hannibal, and M. U. Gillette. PACAP: a pivotal modulator of glutamatergic regulation of the suprachiasmatic circadian clock.  PNAS.  96 (1999), 13468-73.

7.            S. Sheng, S. Hu, J. M. Ding, C.C. Chao, and P.K. Peterson. Cytokine expression in the mouse brain in response to immune activation by corynebacterium parvum. Clinical Diagnostic and Laboratory Immunology.  8 (2000) 446-8.

8.            L. R. Artinia, J. M. Ding, and M. U. Gillette.  Carbon monoxide and nitric oxide: interacting messengers in muscarinic singnaling to the brain's circadian clock.  Experimental Neurology. 171 (2001) 293-300.

9.            J.P. Clark, C. B. Sampair, P. Kofuji, A. Nath, and J. M. Ding. HIV Protein, Transactivator of Transcription, Alters Circadian Rhythms through the Light Entrainment Pathway.  American Journal of Physiology. 289 (2005) R656-662.

10.          S. Michelle, J. P. Clark, J. M. Ding, and C. Colwell.  BDNF induces light-like phase shift of the circadian clock through activation of Glutamate receptor.  European Journal of Neuroscience. 24 (2006) 1109-1116.

11.          Wang X, Wang Y, Xin H, Liu Y, Wang Y, Zheng H, Jiang Z, Wan C, Wang Z, Ding J. M.  Altered expression of circadian clock gene, mPer1, in mouse brain and kidney under morphine dependence and withdrawal. J Circadian Rhythms. 2006 Aug 22;4:9.

12.          Gao X, Xu X, Pang J, Zhang C, Ding J. M., Peng X, Liu Y, Cao JM.  NMDA receptor activation induces mitochondrial dysfunction, oxidative stress and apoptosis in cultured neonatal rat cardiomyocytes. Physiol Res. 56(2007):559-69.

13.          Hua H, Wang Y, Wan C, Liu Y, Zhu B, Wang X, Wang Z, Ding J. M.  Inhibition of tumorigenesis by intratumoral delivery of the circadian gene mPer2 in C57BL/6 mice. Cancer Gene Ther. 14 (2007):815-8.

14.          Li R, Yue J, Zhang Y, Zhou L, Hao W, Yuan J, Qiang B, Ding JM, Peng X, Cao JM.  CLOCK/BMAL1 regulates human nocturnin transcription through binding to the E-box of nocturnin promoter. Mol Cell Biochem. 317 (2008):169-77.

 

Ongoing Support

1R01NS064879-01A110 9/30/2009-8/31/2013

NINDS

Alteration of circadian rhythm and sleep by HIV protein Tat

Role: principal investigator

 

Completed Support (last 5 years)

R01 NS47014-01 9/01/2003-8/31/2008

NINDS

Dysregulation of circadian rhythm by HIV protein TAT

Role: Principal Investigator

2001-2006       NIH study section member

2004-present   Foreign editor for the Chinese Medical Journal: Basic Medicine and Clinics

2007-present   Editorial Board Member: Retrovirology: Research and Treatment