Neurobiology of Circadian Systems

Schulz, Pierre; Steimer, Thierry
September 2009
CNS Drugs;2009 Supplement 2, p3
Academic Journal
Time is a dimension tightly associated with the biology of living species. There are cycles of varied lengths in biological activities, from very short (ultradian) rhythms to rhythms with a period of approximately one day (circadian) and rhythms with longer cycles, of a week, a month, a season, or even longer. These rhythms are generated by endogenous biological clocks, i.e. timekeeping structures, rather than being passive reactions to external fluctuations. In mammals, the suprachiasmatic nucleus (SCN) is the major pacemaker. The pineal gland, which secretes melatonin, is the major pacemaker in other phyla. There also exist biological clocks generating circadian rhythms in peripheral tissues, for example the liver. A series of clock genes generates the rhythm through positive and negative feedback effect of proteins on their own synthesis, and this system oscillates with a circadian period. External factors serve as indicators of the astronomical (solar) time and are called zeitgebers, literally time-givers. Light is the major zeitgeber, which resets daily the SCN circadian clock. In the absence of zeitgebers, the circadian rhythm is said to be free running; it has a period that differs from 24 hours. The SCN, together with peripheral clocks, enables a time-related homeostasis, which can become disorganized in its regulation by external factors (light, social activities, food intake), in the coordination and relative phase position of rhythms, or in other ways. Disturbances of rhythms are found in everyday life (jet lag, shift work), in sleep disorders, and in several psychiatric disorders including affective disorders. As almost all physiological and behavioural functions in humans occur on a rhythmic basis, the possibility that advances, delays or desynchronization of circadian rhythms might participate in neurological and psychiatric disorders has been a theme of research. In affective disorders, a decreased circadian amplitude of several rhythms as well as a phase advance or delay have been described, leading to hypotheses about changes in biological clocks themselves or in their sensitivity to environmental factors, such as light or social cues. Molecular genetics studies have suggested the involvement of circadian clock genes, but no tight association has yet been found. Agomelatine is an antidepressant, agonist at melatonergic MT1, MT2 receptors and antagonist at 5-HT2C receptors, and is able to phase advance circadian rhythms in humans. The fact that non-pharmacological (light therapy, sleep deprivation, rhythm therapy) and pharmacological (lithium, antidepressants, agomelatine) therapies of affective disorders influence circadian rhythms indicates that biological clocks play a role in the pathophysiology of these disorders.


Related Articles

  • Diurnal Expression of the Per2 Gene and Protein in the Lateral Habenular Nucleus. Zhigong Zhao; Haiyan Xu; Yongmao Liu; Li Mu; Jinyu Xiao; Hua Zhao // International Journal of Molecular Sciences;Aug2015, Vol. 16 Issue 8, p16740 

    The suprachiasmatic nucleus plays an important role in generating circadian rhythms in mammals. The lateral habenular nucleus (LHb) is closely linked to this structure. Interestingly, the LHb shows a rhythmic firing rate in vivo and in vitro, and sustained oscillation of rhythmic genes in vitro....

  • Mammalian Cultured Cells as a Model System of Peripheral Circadian Clocks. Tsuchiya, Yoshiki; Nishida, Eisuke // Journal of Biochemistry;Dec2003, Vol. 134 Issue 6, p785 

    The mammalian circadian system consists of multiple oscillators with basically hierarchical relationship, in which the hypothalamic suprachiasmatic nucleus (SCN) is the master pacemaker and the other oscillators in the periphery are subordinate. Although peripheral oscillators have been preceded...

  • The chronobiotic properties of melatonin. PĂ©vet, P.; Bothorel, B.; Slotten, H.; Saboureau, M. // Cell & Tissue Research;Jul2002, Vol. 309 Issue 1, p183 

    In mammals, the exact role of melatonin (Mel) in the circadian timing system remains to be determined. However, exogenously administered Mel, as reported in the present mini-review, has been shown to affect the circadian clock. The sites and mechanisms of action involved in this "chronobiotic"...

  • Neurotransmitters of the retino-hypothalamic tract. Hannibal, Jens // Cell & Tissue Research;Jul2002, Vol. 309 Issue 1, p73 

    The brain's biological clock, which, in mammals, is located in the suprachiasmatic nucleus (SCN), generates circadian rhythms in behaviour and physiology. These biological rhythms are adjusted daily (entrained) to the environmental light/dark cycle via a monosynaptic retinofugal pathway, the...

  • CIRCADIAN RHYTHMS. Tatum IV, William O.; Kaplan, Peter W.; Jallon, Pierre // Epilepsy A to Z: A Concise Encyclopedia;2009, p70 

    An encyclopedia entry for "circadian rhythms" is presented. They refer to a biologic pacemaker which regulates physiologic fluctuation based upon a near 24-hour time period. They are found in all organisms, with the most potential stimulus being light. The suprachiasmatic nucleus in the...

  • The mPer2 gene encodes a functional component of the mammalian circadian clock. Zheng, Binhai; Larkin, David W.; Albrecht, Urs; Zhong Sheng Sun; Sage, Marijke; Eichele, Gregor; Cheng Chi Lee; Bradley, Allan // Nature;7/8/1999, Vol. 400 Issue 6740, p169 

    Presents a report that assesses the in vivo function of mPer2 through the generation and characterization of a deletion mutation in the PAS domain of the mouse mPer2 gene. Shorter circadian period for the mutation display of mice homozygous; Diminution of the oscillating expression of both...

  • Central and Peripheral Signals Set the Circadian Liver Clock. Gross, Liza // PLoS Biology;Feb2007, Vol. 5 Issue 2, p131 

    The article presents a synopsis on the research investigating the relationship of the cyclically expressed genes in peripheral tissues of mammals to the local circadian clocks or to the systemic cues that are directly or indirectly controlled by the suprachiasmatic nucleus (SCN). The authors in...

  • What makes biological clock tick? Concar, David // New Scientist;10/26/91, Vol. 132 Issue 1792, p33 

    Explains the mechanisms of the human circadian clock. Effects of light on the circadian rhythm; Discovery of receptors for the enzyme melatonin inside the suprachiasmatic nuclei (SCN) in the hypothalamus; Loss of circadian rhythms in people with tumors near their SCN; Role of melatonin as a...

  • Role of neuropeptide RFRP-3 in circadian rhythm. SETHI, SUMIT; CHATURVEDI, CHANDRA MOHINI // Current Science (00113891);11/10/2015, Vol. 109 Issue 9, p1551 

    The article discusses the role of neuropeptide RFamide-related peptide-3 (RFRP-3) in circadian rhythm. Topics discussed include the fundamental function of circadian rhythm in allowing one's body to foresee the changing environment and the role of the suprachiasmatic nuclei (SCN) in coordinating...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics