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  • The suitability of actigraphy, diary data, and urinary melatonin profiles for quantitative assessment of sleep disturbances in schizophrenia: a case report.

    27 November 2018

    Sleep disruption is a commonly encountered clinical feature in schizophrenic patients, and one important concern is to determine the extent of this disruption under "real" life situations. Simultaneous wrist actigraphy, diary records, and repeated urine collection for urinary 6-sulphatoxymelatonin (aMT6s) profiles are appropriate tools to assess circadian rhythms and sleep patterns in field studies. Their suitability for long-term recordings of schizophrenic patients living in the community has not been evaluated. In this case report, we document long-term simultaneous wrist actigraphy, light detection, repeated urine collection, and diary records as a suitable combination of non-invasive techniques to quantify and assess changes in sleep-wake cycles, light exposure, and melatonin profiles in a schizophrenic patient. The actigraph was well-tolerated by the patient, and compliance to diary records and 48 h urine collection was particularly good with assistance from family members. The data obtained by these techniques are illustrated, and the results reveal remarkable abnormal patterns of rest-activity patterns, light exposure, and melatonin production. We observed various rest-activity patterns, including phase-shifts, highly delayed sleep on- and offsets, and irregular rest-activity phases. The period of the rest-activity rhythm, light-dark cycle, and melatonin rhythm was longer than 24 h. These circadian abnormalities may reinforce the altered sleep patterns and the problems of cognitive function and social engagement associated with schizophrenic.

  • Non-rod, non-cone photoreception in rodents and teleost fish.

    27 November 2018

    Until recently, all ocular photoreception was attributed to the rods and cones of the retina. However, studies on mice lacking rod and cone photoreceptors (rd/rd cl), has shown that these mice can still use their eyes to detect light to regulate their circadian rhythms, suppress pineal melatonin, modify locomotor activity and modulate pupil size. In addition, action spectra for some of these responses have characterized a novel opsin/vitamin A-based photopigment with a lambda(max) approximately 480 nm. Electrophysiological studies have shown that a subset of retinal ganglion cells are intrinsically photosensitive, and melanopsin has been proposed as the photopigment mediating these responses to light. In contrast to mammals, an inner retinal photopigment gene has been identified in teleost fish. Vertebrate ancient (VA) opsin forms a photopigment with a lambda(max) between 460-500 nm, and is expressed in a sub-set of retinal horizontal cells, and cells in the amacrine and ganglion cell layers. Electrophysiological analysis suggests that VA opsin horizontal cells are intrinsically photosensitive and encode irradiance information. In contrast to mammals, however, the function of these novel ocular photoreceptors remains unknown. We compare non-rod, non-cone ocular photoreceptors in mammals and fish, and examine the criteria used to place candidate photopigment molecules into a functional context.

  • Responses to light after retinal degeneration.

    27 November 2018

    Transgenic rodless mice were given 1-h pulses of light of varying brightness at times of the night when they were normally active. The rodless mice showed decreases in locomotor activity during light pulses brighter than 2 lux; these decreases were significantly greater than those in wildtypes (ANOVA, P < 0.01). However, with very dim light, rodless mice showed no changes in activity, whereas wildtype mice actually increased their activity. It is suggested that irradiance detection could be enhanced by absence of image-forming vision. Enhanced inhibition of activity around twilight may be adaptive for mice in some circumstances and so help maintain genes for retinal degeneration in natural populations.

  • Identification of vertebrate deep brain photoreceptors.

    27 November 2018

    Since the beginning of this century evidence has accumulated which demonstrates that nonmammalian vertebrates possess photoreceptors situated deep within the brain. These photoreceptors have been implicated in several different areas of physiology, but in all species examined, they play a critical role in the regulation of circadian and reproductive responses to light. Many attempts have been made to localize these sensory cells over the past 50 years, but until recently all attempts have failed. As a result, this important sensory system remains largely unexplored. Recent attempts to localize these photoreceptors, in a range of vertebrates, using combined antibody and biochemical approaches has met with some success. However, inconsistencies have emerged. Published and preliminary data raise the possibility of several types of encephalic photoreceptor photopigment (cone-like, rod-like or different from both), and depending on species at least two types of photoreceptor cell: CSF-contacting neurons (larval lamprey, reptiles and birds) and classical neurosecretory neurons within the nucleus magnocellularis preopticus (NMPO)(fish and amphibians).

  • Photoreceptors regulating circadian behavior: a mouse model.

    27 November 2018

    Our recent studies have examined circadian photoreception in mice with hereditary retinal disorders (rd/rd and rds/rds). Despite the loss of visual function in these mice, circadian responses to light remain unaffected. Using c-fos expression within the suprachiasmatic nuclei (SCN) as a marker of neural activation of the circadian entrainment pathway, we have found identical levels of Fos in the SCN of rd/rd and +/+ mice in response to retinal illumination. On the basis of action spectrum studies, and measurements of photopigment retinoids using high-pressure liquid chromatography, we believe that the photopigment mediating circadian responses to light is based upon an opsin, and that 11-cis-retinaldehyde is the photopigment chromophore. Preliminary measurements of mouse rod opsin, blue cone, and green-red cone opsin messenger RNA in retinally degenerate mice suggest that none of these opsins is exclusively used to mediate circadian responses to light. Collectively, our data suggest that circadian photoreception can be maintained by a very small number of rod or cone cells without outer segments, or, alternatively, is performed by an unrecognized class of photoreceptive cell within the mammalian retina.

  • The LH-RH system of the male European starling: photoperiod induces changes to a possible multifunctional peptide system.

    27 November 2018

    In many birds reproduction is triggered by long daylengths but, paradoxically, continued exposure to long days leads to photorefractoriness and a complete shut down of the reproductive system. As these effects are thought to be mediated through the secretion of LH-RH, immunocytochemical techniques were used to investigate changes in the LH-RH system when European starlings were exposed to different photoperiods. Starlings exposed to 11L:13D and with mature testes show strong immunostaining both of LH-RH perikarya and fibers. Photosensitive short-day (8L:16D) starlings with undeveloped testes show an almost identical distribution of strongly immunoreactive perikarya but with less dense fibre staining. However, long-day (18L:6D) photorefractory starlings with fully regressed testes, show a profound reduction in LH-RH immunostaining. Perikarya have the same distribution but show a much reduced intensity of staining and fibers had almost entirely disappeared from all regions of the brain. Preliminary observations on the ultrastructure of immunocytochemically identified LH-RH neurones are also reported.

  • Interstitial retinol-binding protein and cellular retinal-binding protein in the mammalian pineal.

    27 November 2018

    Antibodies against bovine interstitial retinol-binding protein (IRBP) and cellular retinal-binding protein (CRA1BP) were used in immunochemical and immunocytochemical studies of the pineal glands of cattle, hamsters and rats (RCS and RCS-rdy+). On immunoblots, IRBP (Mr 144,000) was identified in cattle, hamster and rat pineal extracts. The abundance of IRBP in bovine pineals was 33 +/- 6 ng.mg-1 (mean +/- SD, n = 12) soluble protein. RCS (Royal College of Surgeons) rat pineals gave a strong IRBP reaction on immunoblots, even when virtually no IRBP could be found in the eye due to photoreceptor degeneration. In the hamster retina IRBP immunostaining was distributed throughout the entire interphotoreceptor matrix and the outer segment layer. The pineal also showed strong IRBP-like immunostaining scattered uniformly throughout the gland. Other hamster brain regions showed no specific immunostaining; however, an immunoreactive protein with the same Mr as IRBP was detected on Western blots of bovine cerebral cortex, spinal cord and brainstem soluble proteins. Immunoreactive proteins at lower Mr were also detected in these tissues. CRA1BP immunoreactivity (Mr about 32,000) was observed in immunoblots of bovine, hamster and rat pineal proteins. These findings suggest that some mammalian pinealocytes are related to the retinal cells that contain CRA1BP (i.e. pigment epithelium, Muller cells) while others are related to the photoreceptors, which synthesize IRBP.

  • Photoperiodism in birds.

    27 November 2018

    Birds show a circadian rhythm in melatonin secretion and, as expected, the pattern of output changes with photoperiod. Somewhat surprisingly then, in view of the mechanisms in mammals, birds do not seem to use this seasonal message in the photoperiodic control of reproduction. Some further experiments are needed, however, because in birds the pineal gland is not the only source of melatonin. Another difference from mammals is that birds detect the photoperiodic light not with the retina but by brain photoreceptors, which probably lie in the hypothalamus. An action spectrum for these receptors has now been obtained for the quail and this shows a peak absorption at 492 nm, suggesting that the photoreceptor is rhodopsin-based. The sensitivity of the brain receptors to 500 nm light was calculated at 2 X 10(4) photons mm-2s-1. For light to induce the photoperiodic response it must be interpreted by the bird's clock as a long day. This happens if the light falls 12-20 h after dawn and coincides with a rhythm of photosensitivity. The subsequent neuroendocrine response to the light signal is both precise and relatively long-term. A single 4 h light pulse initiates a wave of gonadotropin secretion lasting for 10 days. The light stimulus can be replaced by a brief (2 min) daily electrical stimulus given to the hypothalamus 10-12 h after dawn. Over the next few years it should be possible to disentangle further the neural processes involved.