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Melatonin is a natural compound, specifically an indoleamine, produced by and found in different organisms including bacteria and eukaryotes. It was discovered by Aaron B. Lerner and colleagues in 1958 as a substance of the pineal gland from cow that could induce skin lightening in common frogs. It was subsequently discovered as a hormone released in the brain at night which controls the sleep–wake cycle in vertebrates. In vertebrates, melatonin is involved in synchronizing circadian rhythms, including sleep–wake timing and blood pressure regulation, and in control of seasonal rhythmicity including reproduction, fattening, moulting and hibernation. Many of its effects are through activation of the melatonin receptors, while others are due to its role as an antioxidant. Its primary function is to defend against oxidative stress in plants and bacteria. Mitochondria are the main cell organelles that produce the antioxidant melatonin, which indicates that melatonin is an "ancient molecule

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Comparison of acute non-visual bright light responses in patients with optic nerve disease, glaucoma and healthy controls

Lorette Leon

This study examined the effect of optic nerve disease, hence retinal ganglion cell loss, on nonvisual functions related to melanopsin signalling. Test subjects were patients with bilateral visual loss and optic atrophy from either hereditary optic neuropathy (n = 11) or glaucoma (n = 11). We measured melatonin suppression, subjective sleepiness and cognitive functions in response to bright light exposure in the evening. We also quantified the post-illumination pupil response to a blue light stimulus. All results were compared to age-matched controls (n = 22). Both groups of patients showed similar melatonin suppression when compared to their controls. Greater melatonin suppression was intra-individually correlated to larger post-illumination pupil response in patients and controls. Only the glaucoma patients demonstrated a relative attenuation of their pupil response. In addition, they were sleepier with slower reaction times during nocturnal light exposure. In conclusion, glaucomatous, but not hereditary, optic neuropathy is associated with reduced acute light effects. At mild to moderate stages of disease, this is detected only in the pupil function and not in responses conveyed via the retinohypothalamic tract such as melatonin suppression.

Nature Publishing Group2015

Circadian and Wake-Dependent Effects on the Pupil Light Reflex in Response to Narrow-Bandwidth Light Pulses

Lorette Leon

PURPOSE. Nonvisual light-dependent functions in humans are conveyed mainly by intrinsically photosensitive retinal ganglion cells, which express melanopsin as photopigment. We aimed to identify the effects of circadian phase and sleepiness across 24 hours on various aspects of the pupil response to light stimulation. METHODS. We tested 10 healthy adults hourly in two 12-hour sessions covering a 24-hour period. Pupil responses to narrow bandwidth red (635 +/- 18 nm) and blue (463 +/- 24 nm) light (duration of 1 and 30 seconds) at equal photon fluxes were recorded, and correlated with salivary melatonin concentrations at the same circadian phases and to subjective sleepiness ratings. The magnitude of pupil constriction was determined from minimal pupil size. The post-stimulus pupil response was assessed from the pupil size at 6 seconds following light offset, the area within the redilation curve, and the exponential rate of redilation. RESULTS. Among the measured parameters, the pupil size 6 seconds after light offset correlated with melatonin concentrations (P < 0.05) and showed a significant modulation over 24 hours with maximal values after the nocturnal peak of melatonin secretion. In contrast, the post-stimulus pupil response following red light stimulation correlated with subjective sleepiness (P < 0.05) without significant changes over 24 hours. CONCLUSIONS. The post-stimulus pupil response to blue light as a marker of intrinsic melanopsin activity demonstrated a circadian modulation. In contrast, the effect of sleepiness was more apparent in the cone contribution to the pupil response. Thus, pupillary responsiveness to light is under influence of the endogenous circadian clock and subjective sleepiness. (Invest Ophthalmol Vis Sci. 2012;53:4546-4555) DOI: 10.1167/iovs.12-9494

Association for Research in Vision and Ophthalmology2012

Efficient transdifferentiation of human dermal fibroblasts into skeletal muscle

Noaf Salah Ali Alwahab

Skeletal muscle holds significant regenerative potential but is incapable of restoring tissue loss caused by severe injury, congenital defects or tumour ablation. Consequently, skeletal muscle models are being developed to study human pathophysiology and regeneration. Their physiological accuracy, however, is hampered by the lack of an easily accessible human cell source that is readily expandable and capable of efficient differentiation. MYOD1, a master gene regulator, induces transdifferentiation of a variety of cell types into skeletal muscle, although inefficiently in human cells. Here we used MYOD1 to establish its capacity to induce skeletal muscle transdifferentiation of human dermal fibroblasts under baseline conditions. We found significant transdifferentiation improvement via transforming growth factor-/activin signalling inhibition, canonical WNT signalling activation, receptor tyrosine kinase binding and collagen type I utilization. Mechanistically, manipulation of individual signalling pathways modulated the transdifferentiation process via myoblast proliferation, lowering the transdifferentiation threshold and inducing cell fusion. Overall, we used transdifferentiation to achieve the robust derivation of human skeletal myotubes and have described the signalling pathways and mechanisms regulating this process. Copyright (c) 2017 John Wiley & Sons, Ltd.

WILEY2018

Circadian rhythm

A circadian rhythm (sərˈkeɪdiən), or circadian cycle, is a natural oscillation that repeats roughly every 24 hours. Circadian rhythms can refer to any process that originates within an organism (i.e.

Serotonin

Serotonin (ˌsɛrəˈtoʊnᵻn,_ˌsɪərə-) or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memo

Pineal gland

The pineal gland (also known as the pineal body, conarium, or epiphysis cerebri) is a small endocrine gland in the brain of most vertebrates. The pineal gland produces melato

BIO-480: Neuroscience: from molecular mechanisms to disease

The goal of the course is to guide students through the essential aspects of molecular neuroscience and neurodegenerative diseases. The student will gain the ability to dissect the molecular basis of disease in the nervous system in order to begin to understand and identify therapeutic strategies.