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Berson, David M. (2007): Phototransduction in ganglion-cell photoreceptors. In: Pflügers Archiv : European

journal of physiology, Jg. 454, H. 5, S. 849–855. Online verfügbar unter doi:10.1007/s00424-007-0242-2.

Abstract A third class of photoreceptors has recently been identified in the mammalianretina. They are a rare cell type within the class of ganglion cells, which are theoutput cells of the retina. These intrinsically photosensitive retinal ganglion cellssupport a variety of physiological responses to daylight, including synchronization ofcircadian rhythms, modulation of melatonin release, and regulation of pupil size.The goal of this review is to summarize what is currently known concerning thecellular and biochemical basis of phototransduction in these cells. I summarize theoverwhelming evidence that melanopsin serves as the photopigment in these cellsand review the emerging evidence that the downstream signaling cascade,including the light-gated channel, might resemble those found in rhabdomericinvertebrate photoreceptors.SchlagwörterAnimals; Humans; Light; Light Signal Transductionphysiology; Photoreceptor Cells,Invertebrateanatomy & histologyphysiology; Photoreceptor Cells,Vertebratecytologyphysiologyradiation effects; Retinal GanglionCellscytologyphysiologyradiation effects; Retinal Pigmentsmetabolismradiationeffects; Rod Opsinsmetabolismradiation effects; Visual Pathwaysanatomy &histologyphysiologyBrainard, G. C. (1979): Pineal research: the decade of transformation. In: Journal of neural transmission.

Supplementum, H. 13, S. 3–10.

Abstract In a little more than a decade (1954--1965), the pineal gland was demonstrated tobe an active neuroendocrine transducer in contrast to a functionless vestige asearlier supposed. The two major contributions which laid the groundwork for thedevelopment of modern pineal science were Kitay and Altschule's book The PinealGland (1954) and Lerner's isolation and structural work on melatonin (1958). AfterLerner's discovery, biochemists, anatomists, and physiologists determined muchabout the structure and function of the pineal gland. In 1965, Wurtman and Axelrodtied this earlier work together by characterizing the pineal as a neuroendocrinetransducer.SchlagwörterAnimals; History, 20th Century; Melatoninmetabolism; Neurophysiologyhistory;Pineal Glandanatomy & histologyphysiology; Serotoninmetabolism; United StatesBrainard, G. C.; Kavet, R.; Kheifets, L. I. (1999): The relationship between electromagnetic field and lightexposures to melatonin and breast cancer risk: a review of the relevant literature. In: Journal of pineal research,

Jg. 26, H. 2, S. 65–100.

Abstract Worldwide, breast cancer is the most common malignancy accounting for 20-32%of all female cancers. This review summarizes the peer-reviewed, published datapertinent to the hypothesis that increased breast cancer in industrialized countries isrelated to the increased use of electricity [Stevens, R.G., S. Davis 1996]. Thathypothesis specifically proposes that increased exposure to light at night andelectromagnetic fields (EMF) reduce melatonin production. Because some studieshave shown that melatonin suppresses mammary tumorigenesis in rats and blocksestrogen-induced proliferation of human breast cancer cells in vitro, it is reasonedthat decreased melatonin production leads to increased risk of breast cancer. Toevaluate this hypothesis, the paper reviews epidemiological data on associationsbetween electricity and breast cancer, and assesses the data on the effects of EMFexposure on melatonin physiology in both laboratory animals and humans. Inaddition, the results on the effects of melatonin on in vivo carcinogenesis in animalsare detailed along with the controlled in vitro studies on melatonin's effects onhuman breast cancer cell lines. The literature is evaluated for strength of evidence,inter-relationships between various lines of evidence, and gaps in our knowledge.Based on the published data, it is currently unclear if EMF and electric lightexposure are significant risk factors for breast cancer, but further study appears

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warranted. Given the ubiquitous nature of EMF and artificial light exposure alongwith the high incidence of breast cancer, even a small risk would have a substantialpublic health impact.SchlagwörterAnimals; Breast Neoplasmsepidemiologyetiology; Breast Neoplasms,Maleepidemiologyetiology; Electromagnetic Fieldsadverse effects; EnvironmentalExposure; Female; Humans; Light; Male; Melatoninphysiology; OccupationalExposureBrainard, G. C.; Matthews, S. A.; Steger, R. W.; Reiter, R. J.; Asch, R. H. (1984): Day:night variations ofmelatonin, 5-hydroxyindole acetic acid, serotonin, serotonin N-acetyltransferase, tryptophan, norepinephrine and

dopamine in the rabbit pineal gland. In: Life sciences, Jg. 35, H. 15, S. 1615–1622.

Abstract Pineal tryptophan, serotonin, serotonin-N-acetyltransferase (NAT), melatonin, 5-hydroxyindole acetic acid (5HIAA), norepinephrine and dopamine were measured in5 castrated rabbits each at 11.00, 00.30 and 03.00 hours. The rabbits were housedin an L:D 14:10 (lights on 07.00 hours). Significant day:night variations were foundin NAT, melatonin, dopamine and norepinephrine. These results were compared todata concerning rhythms of pineal constituents in other species.Schlagwörter Acetyltransferasesmetabolism; Animals; Arylamine N-Acetyltransferasemetabolism;Circadian Rhythm; Dopaminemetabolism; Female; HydroxyindoleaceticAcidmetabolism; Male; Melatoninmetabolism; Norepinephrinemetabolism; PinealGlandmetabolism; Rabbits; Serotoninmetabolism; TryptophanmetabolismBrainard, George C.; Sliney, David; Hanifin, John P.; Glickman, Gena; Byrne, Brenda; Greeson, Jeffrey M. et al.(2008): Sensitivity of the human circadian system to short-wavelength (420-nm) light. In: Journal of biological

rhythms, Jg. 23, H. 5, S. 379–386. Online verfügbar unter doi:10.1177/0748730408323089.

Abstract The circadian and neurobehavioral effects of light are primarily mediated by aretinal ganglion cell photoreceptor in the mammalian eye containing thephotopigment melanopsin. Nine action spectrum studies using rodents, monkeys,and humans for these responses indicate peak sensitivities in the blue region of thevisible spectrum ranging from 459 to 484 nm, with some disagreement in short-wavelength sensitivity of the spectrum. The aim of this work was to quantify thesensitivity of human volunteers to monochromatic 420-nm light for plasmamelatonin suppression. Adult female (n=14) and male (n=12) subjects participatedin 2 studies, each employing a within-subjects design. In a fluence-response study,subjects (n=8) were tested with 8 light irradiances at 420 nm ranging over a 4-logunit photon density range of 10(10) to 10(14) photons/cm(2)/sec and 1 darkexposure control night. In the other study, subjects (n=18) completed an experimentcomparing melatonin suppression with equal photon doses (1.21 x 10(13)photons/cm(2)/sec) of 420 nm and 460 nm monochromatic light and a darkexposure control night. The first study demonstrated a clear fluence-responserelationship between 420-nm light and melatonin suppression (p<0.001) with a half-saturation constant of 2.74 x 10(11) photons/cm(2)/sec. The second study showedthat 460-nm light is significantly stronger than 420-nm light for suppressingmelatonin (p<0.04). Together, the results clarify the visible short-wavelengthsensitivity of the human melatonin suppression action spectrum. This basicphysiological finding may be useful for optimizing lighting for therapeutic and otherapplications.Schlagwörter Adult; Circadian Rhythmradiation effects; Female; Humans; Light; Male;Melatoninmetabolism; Models, Biological; Neurosecretory Systems; Photons; PinealGlandmetabolism; Retinal Ganglion Cellsmetabolism; Vision, OcularBrainard, George C.; Sliney, David; Hanifin, John P.; Glickman, Gena; Byrne, Brenda; Greeson, Jeffrey M. et al.(2008): Sensitivity of the human circadian system to short-wavelength (420-nm) light. In: Journal of biological

rhythms, Jg. 23, H. 5, S. 379–386. Online verfügbar unter doi:10.1177/0748730408323089.

Abstract The circadian and neurobehavioral effects of light are primarily mediated by aretinal ganglion cell photoreceptor in the mammalian eye containing the

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photopigment melanopsin. Nine action spectrum studies using rodents, monkeys,and humans for these responses indicate peak sensitivities in the blue region of thevisible spectrum ranging from 459 to 484 nm, with some disagreement in short-wavelength sensitivity of the spectrum. The aim of this work was to quantify thesensitivity of human volunteers to monochromatic 420-nm light for plasmamelatonin suppression. Adult female (n=14) and male (n=12) subjects participatedin 2 studies, each employing a within-subjects design. In a fluence-response study,subjects (n=8) were tested with 8 light irradiances at 420 nm ranging over a 4-logunit photon density range of 10(10) to 10(14) photons/cm(2)/sec and 1 darkexposure control night. In the other study, subjects (n=18) completed an experimentcomparing melatonin suppression with equal photon doses (1.21 x 10(13)photons/cm(2)/sec) of 420 nm and 460 nm monochromatic light and a darkexposure control night. The first study demonstrated a clear fluence-responserelationship between 420-nm light and melatonin suppression (p<0.001) with a half-saturation constant of 2.74 x 10(11) photons/cm(2)/sec. The second study showedthat 460-nm light is significantly stronger than 420-nm light for suppressingmelatonin (p<0.04). Together, the results clarify the visible short-wavelengthsensitivity of the human melatonin suppression action spectrum. This basicphysiological finding may be useful for optimizing lighting for therapeutic and otherapplications.Schlagwörter Adult; Circadian Rhythmradiation effects; Female; Humans; Light; Male;Melatoninmetabolism; Models, Biological; Neurosecretory Systems; Photons; PinealGlandmetabolism; Retinal Ganglion Cellsmetabolism; Vision, OcularBuijs, Ruud M.; Scheer, Frank A.; Kreier, Felix; Yi, Chunxia; Bos, Nico; Goncharuk, Valeri D.; Kalsbeek, Andries(2006): Organization of circadian functions: interaction with the body. In: Progress in brain research, Jg. 153, S.

341–360. Online verfügbar unter doi:10.1016/S0079-6123(06)53020-1.

Abstract The hypothalamus integrates information from the brain and the body; this activity isessential for survival of the individual (adaptation to the environment) and thespecies (reproduction). As a result, countless functions are regulated byneuroendocrine and autonomic hypothalamic processes in concert with theappropriate behaviour that is mediated by neuronal influences on other brain areas.In the current chapter attention will be focussed on fundamental hypothalamicsystems that control metabolism, circulation and the immune system. Herein asystem is defined as a physiological and anatomical functional unit, responsible forthe organisation of one of these functions. Interestingly probably because thesesystems are essential for survival, their function is highly dependent on each other'sperformance and often shares same hypothalamic structures. The functioning ofthese systems is strongly influenced by (environmental) factors such as the time ofthe day, stress and sensory autonomic feedback and by circulating hormones. Inorder to get insight in the mechanisms of hypothalamic integration we havefocussed on the influence of the biological clock; the suprachiasmatic nucleus(SCN) on processes that are organized by and in the hypothalamus. The SCNimposes its rhythm onto the body via three different routes of communication: 1.Viathe secretion of hormones; 2. via the parasympathetic and 3.via the sympatheticautonomous nervous system. The SCN uses separate connections via either thesympathetic or via the parasympathetic system not only to prepare the body for thecoming change in activity cycle but also to prepare the body and its organs for thehormones that are associated with such change. Up till now relatively little attentionhas been given to the question how peripheral information might be transmittedback to the SCN. Apart from light and melatonin little is known about other systemsfrom the periphery that may provide information to the SCN. In this chapter attentionwill be paid to e.g. the role of the circumventricular organs in passing info to theSCN. Herein especially the role of the arcuate nucleus (ARC) will be highlighted.The ARC is crucial in the maintenance of energy homeostasis as an integrator oflong- and short-term hunger and satiety signals. Receptors for metabolic hormones