Hypocretin
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Hypocretin
Orexin (), also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. The most common form of narcolepsy, type 1, in which the individual experiences brief losses of muscle tone ("drop attacks" or cataplexy), is caused by a lack of orexin in the brain due to destruction of the cells that produce it.Stanford Center for NarcolepsFAQ(retrieved 27-Mar-2012) It exists in the forms of Orexin-A and Orexin-B. There are 50,000–80,000 orexin-producing neurons in the human brain, located predominantly in the perifornical area and lateral hypothalamus. They project widely throughout the central nervous system, regulating wakefulness, feeding, and other behaviours. There are two types of orexin peptide and two types of orexin receptor. Orexin was discovered in 1998 almost simultaneously by two independent groups of researchers working on the rat brain. One group named it orexin, from ''orexis,'' meaning "appetite" in Greek; the other group named it hypo ...
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Orexin-B
Orexin (), also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. The most common form of narcolepsy, type 1, in which the individual experiences brief losses of muscle tone ("drop attacks" or cataplexy), is caused by a lack of orexin in the brain due to destruction of the cells that produce it.Stanford Center for NarcolepsFAQ(retrieved 27-Mar-2012) It exists in the forms of Orexin-A and Orexin-B. There are 50,000–80,000 orexin-producing neurons in the human brain, located predominantly in the perifornical area and lateral hypothalamus. They project widely throughout the central nervous system, regulating wakefulness, feeding, and other behaviours. There are two types of orexin peptide and two types of orexin receptor. Orexin was discovered in 1998 almost simultaneously by two independent groups of researchers working on the rat brain. One group named it orexin, from ''orexis,'' meaning "appetite" in Greek; the other group named it hypo ...
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Orexin-B
Orexin (), also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. The most common form of narcolepsy, type 1, in which the individual experiences brief losses of muscle tone ("drop attacks" or cataplexy), is caused by a lack of orexin in the brain due to destruction of the cells that produce it.Stanford Center for NarcolepsFAQ(retrieved 27-Mar-2012) It exists in the forms of Orexin-A and Orexin-B. There are 50,000–80,000 orexin-producing neurons in the human brain, located predominantly in the perifornical area and lateral hypothalamus. They project widely throughout the central nervous system, regulating wakefulness, feeding, and other behaviours. There are two types of orexin peptide and two types of orexin receptor. Orexin was discovered in 1998 almost simultaneously by two independent groups of researchers working on the rat brain. One group named it orexin, from ''orexis,'' meaning "appetite" in Greek; the other group named it hypo ...
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Narcolepsy
Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affected also experience episodes of sudden loss of muscle strength, known as cataplexy. Narcolepsy paired with cataplexy is evidenced to be an autoimmune disorder. These experiences of cataplexy can be brought on by strong emotions. Less commonly, there may be vivid hallucinations or an inability to move (sleep paralysis) while falling asleep or waking up. People with narcolepsy tend to sleep about the same number of hours per day as people without, but the quality of sleep tends to be lessened. Narcolepsy is a clinical syndrome of hypothalamic disorder, however, the exact cause of narcolepsy is unknown, with potentially several causes. In up to 10% of cases, there is a family history of the disorder. Often, those affected have low levels of ...
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Cataplexy
Cataplexy is a sudden and transient episode of muscle weakness accompanied by full conscious awareness, typically triggered by emotions such as laughing, crying, or terror. Cataplexy affects approximately 70% of people who have narcolepsy, and is caused by an autoimmune destruction of hypothalamic neurons that produce the neuropeptide hypocretin (also called orexin), which regulates arousal and has a role in stabilization of the transition between wake and sleep states. Cataplexy without narcolepsy is rare and the cause is unknown. The term cataplexy originates from the Greek κατά (''kata'', meaning "down"), and πλῆξις (''plēxis'', meaning "strike") and it was first used around 1880 in German physiology literature to describe the phenomenon of tonic immobility also known as "playing possum" (in reference to the opossum's behavior of feigning death when threatened). In the same year the French neuropsychiatrist Jean-Baptiste Gélineau coined the term 'narcolepsy' and ...
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Thomas Kilduff
Thomas S. Kilduff is an American neuroscientist and the director of SRI International's Center for Neuroscience. He specializes in neurobiology related to sleep and wakefulness, and was involved in the discovery of orexin, hypocretin (also known as orexin), a neuropeptide system that is highly involved in wakefulness regulation. His group at SRI International also discovered an unusual neuronal population in the cerebral cortex that is activated during sleep. He is also a consulting professor at the Stanford University School of Medicine's Department of Psychiatry and Behavioral Sciences. Education Kilduff obtained a B.S. from the University of Florida and earned an M.S. and a Ph.D. in biological sciences from Stanford University, where he was also awarded fellowships from the Danforth Foundation, the Grass Foundation, and the National Science Foundation. Career Kilduff was a senior research scientist at Stanford University's Center for Sleep and Circadian Neurobiology. He was al ...
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Lateral Hypothalamus
The lateral hypothalamus (LH), also called the lateral hypothalamic area (LHA), contains the primary orexinergic nucleus within the hypothalamus that widely projects throughout the nervous system; this system of neurons mediates an array of cognitive and physical processes, such as promoting feeding behavior and arousal, reducing pain perception, and regulating body temperature, digestive functions, and blood pressure, among many others. Clinically significant disorders that involve dysfunctions of the orexinergic projection system include narcolepsy, motility disorders or functional gastrointestinal disorders involving visceral hypersensitivity (e.g., irritable bowel syndrome), and eating disorders. The neurotransmitter glutamate and the endocannabinoids (e.g., anandamide) and the orexin neuropeptides orexin-A and orexin-B are the primary signaling neurochemicals in orexin neurons; pathway-specific neurochemicals include GABA, melanin-concentrating hormone, nociceptin, glucos ...
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Wakefulness
Wakefulness is a daily recurring Human brain, brain state and state of consciousness in which an individual is conscious and engages in coherent cognition, cognitive and behavioral responses to the external world. Being awake is the opposite of being asleep, in which most external inputs to the brain are excluded from neural processing. Effects upon the brain The longer the brain has been awake, the greater the synchronous firing rates of cerebral cortex neurons. After sustained periods of sleep, both the speed and synchronicity of the neurons firing are shown to decrease. Another effect of wakefulness is the reduction of glycogen held in the astrocytes, which supply energy to the neurons. Studies have shown that one of sleep's underlying functions is to replenish this glycogen energy source. Maintenance by the brain Wakefulness is produced by a complex interaction between multiple neurotransmitter systems arising in the brainstem and ascending through the midbrain, hypothalam ...
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Orexin-A
Orexin-A, also known as hypocretin-1, is a naturally occurring neuropeptide and orexin isoform. The orexinergic nucleus in the lateral hypothalamus is the primary orexin projection system in the brain. Structure Orexin-A is a peptide composed of 33 amino acids including an N-terminal pyroglutamyl residue and two intramolecular disulfide bridges between cysteine residues in 6 and 12 and 7 and 14 positions. The amino acid sequence is: Pyroglu-Pro-Leu-Pro-Asp-Cys-Cys-Arg-Gln-Lys-Thr-Cys-Ser-Cys-Arg-Leu-Tyr-Glu-Leu-Leu-His-Gly-Ala-Gly-Asn-His-Ala-Ala-Gly-Ile-Leu-Thr-Leu. Mechanism Orexins are highly excitatory neuropeptides that were first discovered in the brains of rats. It is a peptide that is produced by a very small population of cells in the lateral and posterior hypothalamus. Orexins strongly excite various brain nuclei (neurons) to affect an organism's wakefulness by affecting their dopamine, norepinephrine, histamine and acetylcholine systems. These systems work together to s ...
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Hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus is located below the thalamus and is part of the limbic system. In the terminology of neuroanatomy, it forms the ventral part of the diencephalon. All vertebrate brains contain a hypothalamus. In humans, it is the size of an almond. The hypothalamus is responsible for regulating certain metabolic processes and other activities of the autonomic nervous system. It synthesizes and secretes certain neurohormones, called releasing hormones or hypothalamic hormones, and these in turn stimulate or inhibit the secretion of hormones from the pituitary gland. The hypothalamus controls body temperature, hunger, important aspects of parenting and maternal attachment behaviours, thirst, fatigue, sleep, and circadian rhythms. Structure T ...
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Orexin-A
Orexin-A, also known as hypocretin-1, is a naturally occurring neuropeptide and orexin isoform. The orexinergic nucleus in the lateral hypothalamus is the primary orexin projection system in the brain. Structure Orexin-A is a peptide composed of 33 amino acids including an N-terminal pyroglutamyl residue and two intramolecular disulfide bridges between cysteine residues in 6 and 12 and 7 and 14 positions. The amino acid sequence is: Pyroglu-Pro-Leu-Pro-Asp-Cys-Cys-Arg-Gln-Lys-Thr-Cys-Ser-Cys-Arg-Leu-Tyr-Glu-Leu-Leu-His-Gly-Ala-Gly-Asn-His-Ala-Ala-Gly-Ile-Leu-Thr-Leu. Mechanism Orexins are highly excitatory neuropeptides that were first discovered in the brains of rats. It is a peptide that is produced by a very small population of cells in the lateral and posterior hypothalamus. Orexins strongly excite various brain nuclei (neurons) to affect an organism's wakefulness by affecting their dopamine, norepinephrine, histamine and acetylcholine systems. These systems work together to s ...
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Scripps Research Institute
Scripps Research, previously known as The Scripps Research Institute (TSRI), is a nonprofit American medical research facility that focuses on research and education in the biomedical sciences. Headquartered in San Diego, California, the institute has over 170 laboratories employing 2,100 scientists, technicians, graduate students, and administrative and other staff, making it the largest private, non-profit biomedical research organization in the United States and among the largest in the world. The institute holds over 1,100 patents, has produced 11 FDA-approved therapeutics, and has generated over 50 spin-off companies. According to the 2017 Nature Innovation Index, Scripps Research is the #1 most influential research institution in the world. The Scripps Research graduate program is ranked 9th nationally in the biological sciences, 6th for organic chemistry, and 6th for biochemistry. In 2022, their Jupiter, FL campus became a part of the University of Florida. Jupiter-base ...
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Amino Acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha amino acids appear in the genetic code. Amino acids can be classified according to the locations of the core structural functional groups, as Alpha and beta carbon, alpha- , beta- , gamma- or delta- amino acids; other categories relate to Chemical polarity, polarity, ionization, and side chain group type (aliphatic, Open-chain compound, acyclic, aromatic, containing hydroxyl or sulfur, etc.). In the form of proteins, amino acid '' residues'' form the second-largest component (water being the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. It is thought that they played a key role in enabling life ...
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