273 results on '"Howard A. Cooper"'
Search Results
252. Retinohypothalamic pathway: A breach in the law of Newton-Müller-Gudden?
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Howard M. Cooper, Michel Magnin, and Gérard Mick
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Primates ,Decussation ,genetic structures ,media_common.quotation_subject ,Models, Neurological ,Hypothalamus ,Biology ,Visual system ,Functional Laterality ,Retina ,Species Specificity ,medicine ,Animals ,Contrast (vision) ,Visual Pathways ,Molecular Biology ,media_common ,Mammals ,Suprachiasmatic nucleus ,General Neuroscience ,eye diseases ,Unexpected finding ,medicine.anatomical_structure ,Law ,Neurology (clinical) ,medicine.symptom ,Neuroscience ,Binocular vision ,Developmental Biology - Abstract
Theories of binocular vision originally imagined by Newton provided the foundation for subsequent investigations of the visual system by early anatomists and physiologists. These studies led to the widely accepted concept that degree of optic fiber decussation in the chiasm is inversely related to frontal orientation of the optical axes of the eyes (law of Newton-Müller-Gudden). A survey of 23 species from 11 mammalian orders demonstrates that, in contrast to other visual pathways, the retinohypothalamic projection does not obey this general principle. In further contradiction, an unexpected finding in primates is the predominance of ipsilateral, rather than contralateral, retinal input to the suprachiasmatic nucleus. This unusual organization underlines the functional and evolutionary specificities of this 'non-image forming' visual pathway.
- Published
- 1989
253. Accessory optic system of an anthropoid primate, the gibbon (Hylobates concolor): Evidence of a direct retinal input to the medial terminal nucleus
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Howard M. Cooper and Michel Magnin
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Primates ,Retina ,biology ,Optic tract ,General Neuroscience ,Cerebral peduncle ,Hominidae ,Anatomy ,biology.organism_classification ,Biological Evolution ,Pons ,Midbrain ,medicine.anatomical_structure ,Species Specificity ,Cytoarchitecture ,Mesencephalon ,Fasciculus ,medicine ,Animals ,Hylobates ,Visual Pathways ,Nucleus ,Neuroscience - Abstract
The accessory optic system (AOS) was studied in an anthropoid primate by using anterograde transport of tritiated amino acids and autoradiographic techniques. The course of the accessory optic tract (AOT) and the retinal projection to the terminal nuclei are described in the gibbon and compared to that of other mammals. The AOT consists of a superior fasciculus, which includes both an anterior and a posterior fiber branch. An inferior fasciculus of the AOT is absent. In contrast to previous reports in haplorhine primates, which describe the AOS as consisting of only the dorsal (DTN) and the lateral (LTN) terminal nuclei, we find that in the gibbon, three cellular groups receive a bilateral projection, predominantly from the contralateral retina. According to cytoarchitecture and topographic location, two of these nuclei correspond to the DTN and the LTN. The third cellular group, situated dorsomedial to the substantia nigra, receives a distinct retinal projection and extends rostrocaudally for 2.0 mm in the mesencephalon. This nucleus is homologous to the dorsal division of the medial terminal nucleus (MTN) in other mammals. There was no evidence for a ventral division of the MTN, which in nonprimates is typically situated at the ventromedial base of the cerebral peduncle. Examination of brain morphology in primates suggests that the ventral division of the MTN has been displaced from its phylogenetically stable location in the medial part of the ventral midbrain to a more dorsal position. This shift appears to be a consequence of the overall morphological influences resulting from the relative enlargement of the pons in this region. The demonstration of a direct retinal projection to the MTN in the gibbon, as well as recent reports in other primates, indicates that a complete AOS consisting of three terminal nuclei is a feature common to all mammals.
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- 1987
254. Separation and characterization of hydroxyl aromatics in complex fractions from nondistillable coal-derived liquids
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Robert J. Hurtubise, Howard A. Cooper, and Howard F. Silver
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medicine.medical_specialty ,Chromatography ,Hydrogen compounds ,business.industry ,Chemistry ,Elution ,Carbochemistry ,Fraction (chemistry) ,Elutriation ,Mass spectrometry ,Analytical Chemistry ,medicine ,Gradient elution ,Organic chemistry ,Coal ,business - Abstract
Complex hydroxyl aromatic fractions isolated from nondistillable coal-derived liquids were separated by a combination of normal-phase and reversed-phase liquid chromatography. The normal-phase chromatographic step effected the separation of hydroxyl aromatics into mono- and dihydroxyl fractions. The mono- and dihydroxyl fractions from the coal-liquid sample were characterized with infrared and field-ionization mass spectrometry (FIMS). A monohydroxyl fraction of oils from a Kentucky coal-liquid sample was separated with an optimized reversed-phase chromatographic system. The monohydroxyl fraction was completely eluted by using a combination of isocratic and gradient elution conditions. The combination of reversed-phase liquid chromatography and FIMS provided a unique method for the characterization of the monohydroxyl fraction of oils from the Kentucky coal-liquid sample.
- Published
- 1986
255. Retinal projection to mammalian telencephalon
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Gérard Mick, Michel Magnin, and Howard M. Cooper
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Telencephalon ,Proline ,Tubercle ,Central nervous system ,Hypothalamus ,Biology ,Tritium ,Retina ,chemistry.chemical_compound ,Species Specificity ,Projection (mathematics) ,Leucine ,medicine ,Animals ,Visual Pathways ,Molecular Biology ,Mammals ,Cerebrum ,General Neuroscience ,Olfactory tubercle ,Optic Nerve ,Retinal ,Anterograde tracing ,medicine.anatomical_structure ,chemistry ,Autoradiography ,Neurology (clinical) ,Neuroscience ,Developmental Biology - Abstract
Retinal projections were studied in species from 8 orders of mammals using anterograde tracing techniques. The olfactory tubercle of basal telencephalon receives a projection from the retina in all animals. In all species the course of labelled fibers is similar and the terminal distribution of label along the internal border of the granular cell layer is restricted to the mediocaudal region of the tubercle. These shared characteristics suggest that this pathway is a typical mammalian feature, possibly providing for convergence of visual and chemosensory information in telencephalon.
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- 1989
256. Discussion of 'Mavis on Flow Characteristics in Elbow Draft-Tubes'
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Ellery R. Fosdick, R. E. B. Sharp, Howard L. Cooper, F. T. Mavis, L. F. Harza, and Jerome Fee
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Engineering ,medicine.anatomical_structure ,Flow (mathematics) ,business.industry ,Hull ,Elbow ,Forensic engineering ,medicine ,business ,Civil engineering - Published
- 1938
257. A common mammalian plan of accessory optic system organization revealed in all primates
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M. Magnin and Howard M. Cooper
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Neurons ,Primates ,Vestibular system ,Retina ,Multidisciplinary ,Visual perception ,Central nervous system ,Retinal ,Anatomy ,Biology ,Axonal Transport ,Visual field ,Midbrain ,chemistry.chemical_compound ,medicine.anatomical_structure ,Species Specificity ,chemistry ,Cats ,medicine ,Animals ,Visual Pathways ,Nucleus ,Vision, Ocular - Abstract
The accessory optic system (AOS), which was described as ear ly as 1870 by Gudden1, constitutes a distinct midbrain visual pathway in all classes of vertebrates2. In non-primate mammals, retinal fibres of this system project to a set of three nuclei3,4: the dorsal (DTN), the lateral (LTN) and the medial (MTN) terminal nuclei. Whereas all AOS cells respond to the slow motion of large visual stimuli, the neurons are tuned to complementary directions of movement5: horizontal temporo-nasal direction for the DTN, vertical up and down for the LTN and vertical down for the MTN. It has thus been suggested that these nuclei establish a system of retinal coordinates for the detection of whole field motion6. As the AOS provides direct and indirect pathways to both oculomotor and vestibular structures7,8, each of these nuclei is thought to be an essential link in the co-ordination of eye and head movements in relation to movement within the visual field. One problem for the generalization of this theory is that the medial terminal nucleus has never been found in primates. In this report we establish both the existence of this nucleus and its afferent input from the retina in all major groups of primates (prosimians, New and Old World monkeys and apes), indicating a common anatomical plan of organization of the AOS in mammals.
- Published
- 1986
258. Thalamic projections to area 17 in a prosimian primate, Microcebus murinus
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Henry Kennedy, F. Vital‐Durand, Michel Magnin, and Howard M. Cooper
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Retina ,Brain Mapping ,Microcebus murinus ,genetic structures ,biology ,General Neuroscience ,Thalamus ,Geniculate Bodies ,Anatomy ,biology.organism_classification ,Strepsirhini ,Meridian (perimetry, visual field) ,medicine.anatomical_structure ,Cytoarchitecture ,Receptive field ,Thalamic Nuclei ,Geniculate ,Axoplasmic transport ,medicine ,Visual Perception ,Animals ,Visual Pathways ,Neuroscience ,Visual Cortex - Abstract
Electrophysiological recording of single neurons was used to describe the representation of visual space in area 17, and the technique of retrograde transport of horseradish peroxidase (HRP) was applied to relate these results to projections from the thalamus in the prosimian primate Microcebus murinus. The visuotopic organization of area 17 was found to resemble that of other primates. On the dorsal surface, the border of area 17 corresponds to the representation of the vertical meridian. Proceeding medially across the surface the location of receptive fields descends along the vertical meridian, while moving caudally receptive fields progress temporally. Most of the dorsolateral surface is devoted to central vision and corresponds to a well developed area centralis. Following HRP injections in striate cortex, columns of labeled cells were found in the dorsal lateral geniculate (dLGN) extending orthogonally across all six layers. These columns run in a general ventrodorsal and caudorostral direction, parallel to a line connecting the cellular discontinuities corresponding to the optic disc. These discontinuities are present in magnocellular layer 1 and parvocellualr layers 5 and 6, thus receiving from the nasal retina of the contralateral eye. The representation of the vertical meridian is situated in the ventromedial portion of the dLGN, and the monocular field is represented in the dorsal extremity. Anterior dLGN projects to the calcarine fissure (lower field). and posterior dLGN projects to the ventral surface of the cortex (upper field). Exptrgeniculate input to area 17 was found to originate from the pulvinar. HRP labeled cells were located in two distinct divisions of this nucleus, the cytoarchitecture of which is described. In addition, projections to occipital cortex were found to arise form the intralaminar nuclei.
- Published
- 1979
259. Problems in application of the basic criteria of schizophrenia
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Howard N. Cooper
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Psychiatry and Mental health ,medicine.medical_specialty ,Schizophrenia (object-oriented programming) ,Id, ego and super-ego ,medicine ,Schizophrenia ,Humans ,Psychiatry ,Psychology ,Neuroticism ,Psychopathology - Abstract
Four cases were diagnosed as schizophrenic by careful observation and documentation. The patients had the following in common: 1. By all symptoms no schizophrenia was immediately apparent. It required time and attention to establish the diagnosis in all cases. But then it remained firmly established by the basic accepted criteria. 2. The patients were persons of good intelligence and had other assets as well. They tended to mobilize many mechanisms of defense as "ego" structure threatened to "weaken" further. These consisted both of additional neurotic defenses and some tendency toward "acting-out," but no change was manifested in areas considered schizophrenic. Therefore, we are considering a category of individuals who belong to the group of schizophrenias according to legitimate definition, but apparently no more capable of disorganization, or display of blatant "accessory" symptoms, than the next person. In each of these instances, schizophrenic psychopathology comprised one part of the total picture,...
- Published
- 1960
260. A Microcomputer Data Acquisition-Telemetry System: A Study of Activity in the Bat
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Howard M. Cooper and Pierre Charles-Dominique
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Data acquisition ,Ecology ,Computer science ,Telemetry ,Microcomputer ,General Earth and Planetary Sciences ,Ecology, Evolution, Behavior and Systematics ,System a ,Nature and Landscape Conservation ,General Environmental Science ,Remote sensing - Abstract
Description d'un systeme automatique d'acquisition de donnees sur les deplacements animaux par radiotelemetrie. Application aux chauves-souris en saison des pluies en Guyane francaise
- Published
- 1985
261. A simple electrocardiographic method to predict patency of the infarct-related artery after fibrinolytic therapy
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Marc S. Sabatine, Howard A. Cooper, David A. Morrow, Graham C. Wong, Michael Gibson, Carolyn H. McCabe, Sabina A. Murphy, Eugene Braunwald, Elliott M. Antman, Robert P. Giugliano, and James deLemos
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medicine.medical_specialty ,business.industry ,fungi ,macromolecular substances ,biochemical phenomena, metabolism, and nutrition ,body regions ,Internal medicine ,Cardiology ,Medicine ,Infarct related artery ,Fibrinolytic therapy ,sense organs ,business ,Cardiology and Cardiovascular Medicine - Full Text
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262. 1060-79 Predictors of life-threatening ventricular arrhythmias in high-risk patients with ST elevation acute myocardial infarction
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Sonja M. McKinlay, R. Scott Wright, Susan F. Assmann, Judith S. Hochman, Elliott M. Antman, Howard A. Cooper, Bernard J. Gersh, and Michael Domanksi
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medicine.medical_specialty ,High risk patients ,business.industry ,Internal medicine ,ST elevation ,medicine ,Cardiology ,Electrocardiography in myocardial infarction ,Myocardial infarction ,medicine.disease ,business ,Cardiology and Cardiovascular Medicine - Full Text
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263. ARRHYTHMIAS AND ASSOCIATED OUTCOMES IN ADULTS WITH CONGENITAL HEART DISEASE IN THE UNITED STATES
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Sei Iwai, Ali Ahmed, Sachin Sule, William H. Frishman, Howard A. Cooper, Julio A. Panza, Marjan Mujib, Jason T. Jacobson, Wilbert S. Aronow, Diwakar Jain, Dhaval Kolte, Prakash Harikrishnan, Chandrasekar Palaniswamy, Sahil Khera, and Gregg Fonarow
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medicine.medical_specialty ,Heart disease ,business.industry ,medicine ,cardiovascular diseases ,Intensive care medicine ,medicine.disease ,business ,Cardiology and Cardiovascular Medicine - Full Text
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264. TCT-290 Fractional Flow Reserve Measurement in Non-ST-Elevation Myocardial Infarction: Analysis of the National Inpatient Sample Database
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Wilbert S. Aronow, Robert Timmermans, Prakash Harikrishnan, Howard A. Cooper, Julio A. Panza, Chandrasekar Palaniswamy, Nivas Balasubramaniyam, Hasan Ahmad, and Tanush Gupta
- Subjects
medicine.medical_specialty ,business.industry ,St elevation myocardial infarction ,Internal medicine ,medicine ,Cardiology ,Physical therapy ,Sample (statistics) ,Fractional flow reserve ,Cardiology and Cardiovascular Medicine ,business - Full Text
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265. Induced Cognitive Impairments Reversed by Grafts of Neural Precursors: A Longitudinal Study in a Macaque Model of Parkinson's Disease
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Florence Wianny, Kwamivi Dzahini, Karim Fifel, Charles Robert Eden Wilson, Agnieszka Bernat, Virginie Dolmazon, Pierre Misery, Camille Lamy, Pascale Giroud, Howard Michael Cooper, Kenneth Knoblauch, Emmanuel Procyk, Henry Kennedy, Pierre Savatier, Colette Dehay, and Julien Vezoli
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circadian rhythms ,cognition and motor control ,embryonic stem cells ,neural precursors ,nonhuman primate low‐dose MPTP ,Science - Abstract
Abstract Parkinson's disease (PD) evolves over an extended and variable period in humans; years prior to the onset of classical motor symptoms, sleep and biological rhythm disorders develop, significantly impacting the quality‐of‐life of patients. Circadian‐rhythm disorders are accompanied by mild cognitive deficits that progressively worsen with disease progression and can constitute a severe burden for patients at later stages. The gold‐standard 6‐methyl‐1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridin (MPTP) macaque model of PD recapitulates the progression of motor and nonmotor symptoms over contracted periods of time. Here, this multidisciplinary/multiparametric study follows, in five animals, the steady progression of motor and nonmotor symptoms and describes their reversal following grafts of neural precursors in diverse functional domains of the basal ganglia. Results show unprecedented recovery from cognitive symptoms in addition to a strong clinical motor recuperation. Both motor and cognitive recovery and partial circadian rhythm recovery correlate with the degree of graft integration, and in a subset of animals, with in vivo levels of striatal dopaminergic innervation and function. The present study provides empirical evidence that integration of neural precursors following transplantation efficiently restores function at multiple levels in parkinsonian nonhuman primates and, given interindividuality of disease progression and recovery, underlines the importance of longitudinal multidisciplinary assessments in view of clinical translation.
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- 2022
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266. Rods contribute to the light-induced phase shift of the retinal clock in mammals.
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Hugo Calligaro, Christine Coutanson, Raymond P Najjar, Nadia Mazzaro, Howard M Cooper, Nasser Haddjeri, Marie-Paule Felder-Schmittbuhl, and Ouria Dkhissi-Benyahya
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Biology (General) ,QH301-705.5 - Abstract
While rods, cones, and intrinsically photosensitive melanopsin-containing ganglion cells (ipRGCs) all drive light entrainment of the master circadian pacemaker of the suprachiasmatic nucleus, recent studies have proposed that entrainment of the mouse retinal clock is exclusively mediated by a UV-sensitive photopigment, neuropsin (OPN5). Here, we report that the retinal circadian clock can be phase shifted by short duration and relatively low-irradiance monochromatic light in the visible part of the spectrum, up to 520 nm. Phase shifts exhibit a classical photon dose-response curve. Comparing the response of mouse models that specifically lack middle-wavelength (MW) cones, melanopsin, and/or rods, we found that only the absence of rods prevented light-induced phase shifts of the retinal clock, whereas light-induced phase shifts of locomotor activity are normal. In a "rod-only" mouse model, phase shifting response of the retinal clock to light is conserved. At shorter UV wavelengths, our results also reveal additional recruitment of short-wavelength (SW) cones and/or OPN5. These findings suggest a primary role of rod photoreceptors in the light response of the retinal clock in mammals.
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- 2019
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267. Loss of dopamine disrupts circadian rhythms in a mouse model of Parkinson's disease
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Karim Fifel and Howard M. Cooper
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Dopamine ,Striatum ,Sleep ,Parkinson ,Suprachiasmatic nucleus ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Although a wide range of physiological functions regulated by dopamine (DA) display circadian variations, the role of DA in the generation and/or modulation of these rhythms is unknown. In Parkinson's disease (PD) patients, in addition to the classical motor symptoms, disturbances of the pattern of daily rest/wake cycles are common non-motor symptoms. We investigated daily and circadian rhythms of rest/activity behaviors in a transgenic MitoPark mouse model with selective inactivation of mitochondrial transcription factor A (Tfam) resulting in a slow and progressive degeneration of DA neurons in midbrain structures. Correlated with this, MitoPark mice show a gradual reduction in locomotor activity beginning at about 20 weeks of age. In a light–dark cycle, MitoPark mice exhibit a daily pattern of rest/activity rhythms that shows an age-dependent decline in both the amplitude and the stability of the rhythm, coupled with an increased fragmentation of day/night activities. When the circadian system is challenged by exposure to constant darkness or constant light conditions, control littermates retain a robust free-running circadian locomotor rhythm, whereas in MitoPark mice, locomotor rhythms are severely disturbed or completely abolished. Re-exposure to a light/dark cycle completely restores daily locomotor rhythms. MitoPark mice and control littermates express similar masking behaviors under a 1 h light/1 h dark regime, suggesting that the maintenance of a daily pattern of rest/activity in arrhythmic MitoPark mice can be attributed to the acute inhibitory and stimulatory effects of light and darkness. These results imply that, in addition to the classical motor abnormalities observed in PD, the loss of the midbrain DA neurons leads to impairments of the circadian control of rest/activity rhythms.
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- 2014
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268. Aging of non-visual spectral sensitivity to light in humans: compensatory mechanisms?
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Raymond P Najjar, Christophe Chiquet, Petteri Teikari, Pierre-Loïc Cornut, Bruno Claustrat, Philippe Denis, Howard M Cooper, and Claude Gronfier
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Medicine ,Science - Abstract
The deterioration of sleep in the older population is a prevalent feature that contributes to a decrease in quality of life. Inappropriate entrainment of the circadian clock by light is considered to contribute to the alteration of sleep structure and circadian rhythms in the elderly. The present study investigates the effects of aging on non-visual spectral sensitivity to light and tests the hypothesis that circadian disturbances are related to a decreased light transmittance. In a within-subject design, eight aged and five young subjects were exposed at night to 60 minute monochromatic light stimulations at 9 different wavelengths (420-620 nm). Individual sensitivity spectra were derived from measures of melatonin suppression. Lens density was assessed using a validated psychophysical technique. Although lens transmittance was decreased for short wavelength light in the older participants, melatonin suppression was not reduced. Peak of non-visual sensitivity was, however, shifted to longer wavelengths in the aged participants (494 nm) compared to young (484 nm). Our results indicate that increased lens filtering does not necessarily lead to a decreased non-visual sensitivity to light. The lack of age-related decrease in non-visual sensitivity to light may involve as yet undefined adaptive mechanisms.
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- 2014
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269. Alteration of daily and circadian rhythms following dopamine depletion in MPTP treated non-human primates.
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Karim Fifel, Julien Vezoli, Kwamivi Dzahini, Bruno Claustrat, Vincent Leviel, Henry Kennedy, Emmanuel Procyk, Ouria Dkhissi-Benyahya, Claude Gronfier, and Howard M Cooper
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Medicine ,Science - Abstract
Disturbances of the daily sleep/wake cycle are common non-motor symptoms of Parkinson's disease (PD). However, the impact of dopamine (DA) depletion on circadian rhythms in PD patients or non-human primate (NHP) models of the disorder have not been investigated. We evaluated alterations of circadian rhythms in NHP following MPTP lesion of the dopaminergic nigro-striatal system. DA degeneration was assessed by in vivo PET ([(11)C]-PE2I) and post-mortem TH and DAT quantification. In a light∶dark cycle, control and MPTP-treated NHP both exhibit rest-wake locomotor rhythms, although DA-depleted NHP show reduced amplitude, decreased stability and increased fragmentation. In all animals, 6-sulphatoxymelatonin peaks at night and cortisol in early morning. When the circadian system is challenged by exposure to constant light, controls retain locomotor rest-wake and hormonal rhythms that free-run with stable phase relationships whereas in the DA-depleted NHP, locomotor rhythms are severely disturbed or completely abolished. The amplitude and phase relations of hormonal rhythms nevertheless remain unaltered. Use of a light-dark masking paradigm shows that expression of daily rest-wake activity in MPTP monkeys requires the stimulatory and inhibitory effects of light and darkness. These results suggest that following DA lesion, the central clock in the SCN remains intact but, in the absence of environmental timing cues, is unable to drive downstream rhythmic processes of striatal clock gene and dopaminergic functions that control locomotor output. These findings suggest that the circadian component of the sleep-wake disturbances in PD is more profoundly affected than previously assumed.
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- 2014
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270. Clock genes and behavioral responses to light are altered in a mouse model of diabetic retinopathy.
- Author
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Hasna Lahouaoui, Christine Coutanson, Howard M Cooper, Mohamed Bennis, and Ouria Dkhissi-Benyahya
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Medicine ,Science - Abstract
There is increasing evidence that melanopsin-expressing ganglion cells (ipRGCs) are altered in retinal pathologies. Using a streptozotocin-induced (STZ) model of diabetes, we investigated the impact of diabetic retinopathy on non-visual functions by analyzing ipRGCs morphology and light-induced c-Fos and Period 1-2 clock genes in the central clock (SCN). The ability of STZ-diabetic mice to entrain to light was challenged by exposure animals to 1) successive light/dark (LD) cycle of decreasing or increasing light intensities during the light phase and 2) 6-h advance of the LD cycle. Our results show that diabetes induces morphological changes of ipRGCs, including soma swelling and dendritic varicosities, with no reduction in their total number, associated with decreased c-Fos and clock genes induction by light in the SCN at 12 weeks post-onset of diabetes. In addition, STZ-diabetic mice exhibited a reduction of overall locomotor activity, a decrease of circadian sensitivity to light at low intensities, and a delay in the time to re-entrain after a phase advance of the LD cycle. These novel findings demonstrate that diabetes alters clock genes and behavioral responses of the circadian timing system to light and suggest that diabetic patients may show an increased propensity for circadian disturbances, in particular when they are exposed to chronobiological challenges.
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- 2014
- Full Text
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271. Early presymptomatic and long-term changes of rest activity cycles and cognitive behavior in a MPTP-monkey model of Parkinson's disease.
- Author
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Julien Vezoli, Karim Fifel, Vincent Leviel, Colette Dehay, Henry Kennedy, Howard M Cooper, Claude Gronfier, and Emmanuel Procyk
- Subjects
Medicine ,Science - Abstract
BACKGROUND: It is increasingly recognized that non-motor symptoms are a prominent feature of Parkinson's disease and in the case of cognitive deficits can precede onset of the characteristic motor symptoms. Here, we examine in 4 monkeys chronically treated with low doses of the neurotoxin MPTP the early and long-term alterations of rest-activity rhythms in relationship to the appearance of motor and cognitive symptoms. METHODOLOGY/PRINCIPAL FINDINGS: Behavioral activity recordings as well as motor and cognitive assessments were carried out continuously and in parallel before, during and for several months following MPTP-treatment (12-56 weeks). Cognitive abilities were assessed using a task that is dependent on the functional integrity of the fronto-striatal axis. Rest-activity cycles were monitored continuously using infrared movement detectors of locomotor activity. Motor impairment was evaluated using standardized scales for primates. Results show that MPTP treatment led to an immediate alteration (within one week) of rest-activity cycles and cognitive deficits. Parkinsonian motor deficits only became apparent 3 to 5 weeks after initiating chronic MPTP administration. In three of the four animals studied, clinical scores returned to control levels 5-7 weeks following cessation of MPTP treatment. In contrast, both cognitive deficits and chronobiological alterations persisted for many months. Levodopa treatment led to an improvement of cognitive performance but did not affect rest-activity rhythms in the two cases tested. CONCLUSIONS/SIGNIFICANCE: Present results show that i) changes in the rest activity cycles constituted early detectable consequences of MPTP treatment and, along with cognitive alterations, characterize the presymptomatic stage; ii) following motor recovery there is a long-term persistence of non-motor symptoms that could reflect differential underlying compensatory mechanisms in these domains; iii) the progressive MPTP-monkey model of presymptomatic ongoing parkinsonism offers possibilities for in-depth studies of early non-motor symptoms including sleep alterations and cognitive deficits.
- Published
- 2011
- Full Text
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272. Melanopsin bistability: a fly's eye technology in the human retina.
- Author
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Ludovic S Mure, Pierre-Loic Cornut, Camille Rieux, Elise Drouyer, Philippe Denis, Claude Gronfier, and Howard M Cooper
- Subjects
Medicine ,Science - Abstract
In addition to rods and cones, the human retina contains light-sensitive ganglion cells that express melanopsin, a photopigment with signal transduction mechanisms similar to that of invertebrate rhabdomeric photopigments (IRP). Like fly rhodopsins, melanopsin acts as a dual-state photosensitive flip-flop in which light drives both phototransduction responses and chromophore photoregeneration that bestows independence from the retinoid cycle required by rods and cones to regenerate photoresponsiveness following bleaching by light. To explore the hypothesis that melanopsin in humans expresses the properties of a bistable photopigment in vivo we used the pupillary light reflex (PLR) as a tool but with methods designed to study invertebrate photoreceptors. We show that the pupil only attains a fully stabilized state of constriction after several minutes of light exposure, a feature that is consistent with typical IRP photoequilibrium spectra. We further demonstrate that previous exposure to long wavelength light increases, while short wavelength light decreases the amplitude of pupil constriction, a fundamental property of IRP difference spectra. Modelling these responses to invertebrate photopigment templates yields two putative spectra for the underlying R and M photopigment states with peaks at 481 nm and 587 nm respectively. Furthermore, this bistable mechanism may confer a novel form of "photic memory" since information of prior light conditions is retained and shapes subsequent responses to light. These results suggest that the human retina exploits fly-like photoreceptive mechanisms that are potentially important for the modulation of non-visual responses to light and highlights the ubiquitous nature of photoswitchable photosensors across living organisms.
- Published
- 2009
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273. Glaucoma alters the circadian timing system.
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Elise Drouyer, Ouria Dkhissi-Benyahya, Christophe Chiquet, Elizabeth WoldeMussie, Guadalupe Ruiz, Larry A Wheeler, Philippe Denis, and Howard M Cooper
- Subjects
Medicine ,Science - Abstract
Glaucoma is a widespread ocular disease and major cause of blindness characterized by progressive, irreversible damage of the optic nerve. Although the degenerative loss of retinal ganglion cells (RGC) and visual deficits associated with glaucoma have been extensively studied, we hypothesize that glaucoma will also lead to alteration of the circadian timing system. Circadian and non-visual responses to light are mediated by a specialized subset of melanopsin expressing RGCs that provide photic input to mammalian endogenous clock in the suprachiasmatic nucleus (SCN). In order to explore the molecular, anatomical and functional consequences of glaucoma we used a rodent model of chronic ocular hypertension, a primary causal factor of the pathology. Quantitative analysis of retinal projections using sensitive anterograde tracing demonstrates a significant reduction (approximately 50-70%) of RGC axon terminals in all visual and non-visual structures and notably in the SCN. The capacity of glaucomatous rats to entrain to light was challenged by exposure to successive shifts of the light dark (LD) cycle associated with step-wise decreases in light intensity. Although glaucomatous rats are able to entrain their locomotor activity to the LD cycle at all light levels, they require more time to re-adjust to a shifted LD cycle and show significantly greater variability in activity onsets in comparison with normal rats. Quantitative PCR reveals the novel finding that melanopsin as well as rod and cone opsin mRNAs are significantly reduced in glaucomatous retinas. Our findings demonstrate that glaucoma impacts on all these aspects of the circadian timing system. In light of these results, the classical view of glaucoma as pathology unique to the visual system should be extended to include anatomical and functional alterations of the circadian timing system.
- Published
- 2008
- Full Text
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