Circadian rhythm neurotransmitters

Jacobs, EH, Yamatodani, A and Timmerman, H (2000) Is histamine the final neurotransmitter in the entrainment of circadian rhythms TIPS 21 293-298. 

Furthermore, many of these neurotransmitters subserve or intimately interact with a number of neuroendocrine, circadian rhythm, and neurophysiological activities, which may be dysregulated in mood disorders. Genetic defects are quite likely the basis for such pathology. 

One of the most consistent findings is the sleep disturbance that often precedes and may even trigger a manic phase ( 46). Studies on circadian rhythms have demonstrated that many aspects of the sleep cycle are phase-advanced in mania (i.e., occur earlier than normal), and often these patterns resemble the free-running rhythms seen in normal individuals who are removed from all time cues. In addition, there is a blunting of amplitude and a doubling of the sleep-wake cycle up to 48 hours. Lithium is known to delay the sleep-wake cycle and often slow such free-running rhythms, which in turn are partly modulated by neurotransmitters such as NE, 5-HT, and acetylcholine. Further, manipulation of the sleep-wake cycle may prevent a manic episode or be used to treat the depressive phase (e.g., sleep deprivation therapy see also the section Experiments in Chapter 8). 

Autonomous functions, especially the circadian rhythms of sleep-wake cycles and cortisol release, are significantly disturbed during depression. However, it is still unclear whether these circadian alterations are reliably linked with psychopathology and whether they provide clues to the underlying mechanism, in particular with respect to the neurotransmitter models of depression [8] and the CRH-overdrive hypothesis [29]. 

Focusing our attention on the serotonin branch of Figure 20.21, it is seen that the initial hydroxylation reaction requires tetrahydrobiopterin, which was introduced in Chapter 16 and is discussed further here. Serotonin per se is a neurotransmitter, and it can give rise to melatonin in the pineal gland. Melatonin is synthesized at night, and is believed to be associated with the phenomenon of circadian rhythms. Serotonin is metabolized to 5-hydroxyindoleacetic acid, which is excreted in the urine. Normal 5-hydroxyindoleacetic add excretion is about 7 mg/day, whereas in carcinoid tumor patients, this may be as high as 400 mg/day. Carcinoid is an intestinal tumor that may metastasize into the liver. 

Neuronal projections from the hypothalamus to other regions of the brain relay important output information that influence blood pressure, appetite, thirst, circadian rhythm, behavior, nociception (pain perception), and others factors. Although many of these neurons release neurotransmitter amines at synapses, some of them are known to release neurotransmitter peptides. These include, among others, peptides that closely resemble hormones formed in the gastrointestinal system as well as the endogenous opiates (Table 31-3). 

Li JC, Li YP, Xue LS. Influence of ginseng saponins on the circadian rhythm in brain monoamine neurotransmitters. Presented at the 5th Southeast Asian and Western Pacific Regional Meeting of Pharmacologists, Chinese Pharmacological Association, Beijing, 1988. 

Indole is perhaps the most visible heterocycle in all of chemistry. Since Adolf von Baeyer proposed the structure of indole as a heteroaromatic compound 140 years ago, indole has embodied a myriad of natural products, pharmaceutical agents, and a growing list of polymers. In the human body, serotonin modulates 5-hydroxytryptamine (5-HT), a monoamine neurotransmitter primarily found in the gastrointestinal (GI) tract and central nervous system (CNS), and modulates vasoconstriction and many brain activities. Melatonin regulates circadian rhythms, most noticeably, sleep. Tryptamine is closely related to melatonin and the amino acid tryptophan. 

Jacobs EH, Yamatodani A, Ummerman H. Is histamine the final neurotransmitter in the entrainment of circadian rhythms in mammals Trends Pharmacol Scl, 21 S), 293-298, 2000 Jalan R, Damink SW, Deutz NE, Lee A, Hayes PC. Moderate hypothermia for uncontrolled intracranial hypertension in acute liver failure. Lcmcet, 354(9185), 1164-1168, 1999 Jalan R, Pollok A, Shah SH, Madhavan K, Simpson KJ. Liver derived pro-infltunmatory cytokines may be important in producing intracranial hypertension in ALE J. Hepatol, 37, 536-538, 2002... 

Naturally Occurring Compounds. Many derivatives of iadole are found ia plants and animals where they are derived from the amino acid tryptophan. Several of these have important biological function or activity. Serotonin [50-67-9] (12) functions as a neurotransmitter and vasoconstrictor (35). Melatonin [73-31-4] (13) production is controlled daily by the circadian cycle and its physiological level iafluences, and seasonal rhythms ia humans and other species (36). Indole-3-acetic acid [87-51-4] (14) is a plant growth stimulant used ia several horticultural appHcations (37). 

Kafka M, Wirz-Justice A, Naber D, et al Effect of lithium on circadian neurotransmitter receptor rhythms. Neuropsychobiology 8 41-50, 1982 Kagan J, Reznick JS, Snidman N The physiology and psychology of behavioral inhibition. Child Dev 58 1459-1473, 1987... 

D. melanogaster, PDF is localized in a few specialized neurons which have their cell bodies in the optic lobe and some processes in the accessory medulla of the optic lobe, an area which is known to house the neurons of master circadian pacemakers responsible for daily locomotoiy rhythms [72, 73]. It is from these and a number of other observations that PDFs are thought to be the communicator of these pacemaker cells to spread the message of the biological clock, thus acting as peptidergic neurotransmitters [74]. The PDFs do not affect pigment movement in insects. 

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