Hypocretins/orexins are crucial for the regulation of wakefulness by the excitatory actions on multiple subcortical arousal systems. In prefrontal cortex,
Orexins (or hypocretins) are hypothalamic neuropeptides with a multitude of physiological functions. They occur in two known forms, namely, orexin A and orexin B with a common precursor, preproorexin. The orexin recep...Orexins (or hypocretins) are hypothalamic neuropeptides with a multitude of physiological functions. They occur in two known forms, namely, orexin A and orexin B with a common precursor, preproorexin. The orexin receptors (orexin 1R and orexin 2R) belong to the Family of G-protein coupled receptors. The primary function of the orexin system,i.e. the orexins, their receptors and associated neuronal circuitries, perhaps is to increase spontaneous physical activity and food intake, thereby promoting an increase in energy expenditure. Reports suggest that orexins may be the key brain components to mediate the mechanism of obesity resistance. Recent research also has thrown lights upon a significant role of orexins, especially orexin A, in regulation of male reproductive functions owing to their receptor expressions in vital testicular cells, such as Leydig cells, Sertoli cells as well as spermatozoa at different developmental stages, even in the epididymis and penis. Moreover, orexins have been reported to greatly influence gonadotropin-releasing hormone neurons and their secretions to regulate reproductive functionsvia modulation of the hypothalamic-pituitary-gonadal axis. Evidence thus implicates participation of orexins in steroidogenesis, spermatogenesis, transportation and maturation of sperm as well as in the control of penile function. However, further research is required in this direction to elucidate the mechanisms by which orexins play a role in different testicular functions and effect of orexins on semen quality.展开更多
Hypothalamic neuropeptides named hypocretin/orexins which were identified in 1998 regulate critical functions such as wakefulness in the central nervous system.These past 20 years had revealed that orexins/receptors s...Hypothalamic neuropeptides named hypocretin/orexins which were identified in 1998 regulate critical functions such as wakefulness in the central nervous system.These past 20 years had revealed that orexins/receptors system was also present in the peripheral nervous system where they participated to the regulation of multiple functions including blood pressure regulation,intestinal motility,hormone secretion,lipolyze and reproduction functions.Associated to these peripheral functions,it was found that orexins and their receptors were involved in various diseases such as acute/chronic inflammation,metabolic syndrome and cancers.The present review suggests that orexins or the orexin neural circuitry represent potential therapeutic targets for the treatment of multiple pathologies related to inflammation including intestinal bowel disease,multiple sclerosis and septic shock,obesity and digestive cancers.展开更多
Alzheimer's disease(AD) is a growing health problem. It has enormous public health impact. Sleep problems show an early component of this disease. Hypocretin hasa major function in sleep-wake cycle. The total numb...Alzheimer's disease(AD) is a growing health problem. It has enormous public health impact. Sleep problems show an early component of this disease. Hypocretin hasa major function in sleep-wake cycle. The total number of hypocretin neurons in the normal humans ranges from 51000-83000, located exclusively in the hypothalamus. Deficiency in hypocretins neurotransmission results in narcolepsy, Parkinson's disease, and other neurological and psychological disorders. Cerebrospinal fluid(CSF) hypocretin levels were directly related with t-tau protein amount in AD. Increased hypocretin CSF in AD suggest that hypocretin is involved in the mechanism of AD pathology.展开更多
Previous studies have shown that reduced sleep duration,sleep fragmentation,and decreased sleep quality in patients with Alzheimer's disease are related to dysfunction in orexin signaling.At the same time,blood-br...Previous studies have shown that reduced sleep duration,sleep fragmentation,and decreased sleep quality in patients with Alzheimer's disease are related to dysfunction in orexin signaling.At the same time,blood-brain barrier disruption is considered an early biomarker of Alzheimer's disease.However,currently no report has examined how changes in orexin signaling relate to changes in the blood-brain barrier of patients who have Alzheimer's disease with sleep insufficiency.This cross-sectional study included 50 patients with Alzheimer's disease who received treatment in 2019 at Beijing Tiantan Hospital.Patients were divided into two groups:those with insufficient sleep(sleep duration≤6 hours,n=19,age 61.58±8.54 years,10 men)and those with normal sleep durations(sleep duration>6 hours,n=31,age 63.19±10.09 years,18 men).Demographic variables were collected to evaluate cognitive function,neuropsychiatric symptoms,and activities of daily living.The levels of orexin,its receptor proteins,and several blood-brain barrier factors were measured in cerebrospinal fluid.Sleep insufficiency was associated with impaired overall cognitive function that spanned multiple cognitive domains.Furthermore,levels of orexin and its receptors were upregulated in the cerebrospinal fluid,and the blood–brain barrier was destroyed.Both these events precipitated each other and accelerated the progression of Alzheimer's disease.These findings describe the clinical characteristics and potential mechanism underlying Alzheimer's disease accompanied by sleep deprivation.Inhibiting the upregulation of elements within the orexin system or preventing the breakdown of the blood-brain barrier could thus be targets for treating Alzheimer's disease.展开更多
文摘Hypocretins/orexins are crucial for the regulation of wakefulness by the excitatory actions on multiple subcortical arousal systems. In prefrontal cortex,
文摘Orexins (or hypocretins) are hypothalamic neuropeptides with a multitude of physiological functions. They occur in two known forms, namely, orexin A and orexin B with a common precursor, preproorexin. The orexin receptors (orexin 1R and orexin 2R) belong to the Family of G-protein coupled receptors. The primary function of the orexin system,i.e. the orexins, their receptors and associated neuronal circuitries, perhaps is to increase spontaneous physical activity and food intake, thereby promoting an increase in energy expenditure. Reports suggest that orexins may be the key brain components to mediate the mechanism of obesity resistance. Recent research also has thrown lights upon a significant role of orexins, especially orexin A, in regulation of male reproductive functions owing to their receptor expressions in vital testicular cells, such as Leydig cells, Sertoli cells as well as spermatozoa at different developmental stages, even in the epididymis and penis. Moreover, orexins have been reported to greatly influence gonadotropin-releasing hormone neurons and their secretions to regulate reproductive functionsvia modulation of the hypothalamic-pituitary-gonadal axis. Evidence thus implicates participation of orexins in steroidogenesis, spermatogenesis, transportation and maturation of sperm as well as in the control of penile function. However, further research is required in this direction to elucidate the mechanisms by which orexins play a role in different testicular functions and effect of orexins on semen quality.
基金INSERM U1149/The Inflammation Research Center,Inserm Transfert,The Institut National du Cancer,No.2013-213Ligue Nationale Contre le Cancer,No.R16020HH,GB/MA/CD/EP-12062and AgroParisTech(INRAE and UniversitéParis-Saclay).
文摘Hypothalamic neuropeptides named hypocretin/orexins which were identified in 1998 regulate critical functions such as wakefulness in the central nervous system.These past 20 years had revealed that orexins/receptors system was also present in the peripheral nervous system where they participated to the regulation of multiple functions including blood pressure regulation,intestinal motility,hormone secretion,lipolyze and reproduction functions.Associated to these peripheral functions,it was found that orexins and their receptors were involved in various diseases such as acute/chronic inflammation,metabolic syndrome and cancers.The present review suggests that orexins or the orexin neural circuitry represent potential therapeutic targets for the treatment of multiple pathologies related to inflammation including intestinal bowel disease,multiple sclerosis and septic shock,obesity and digestive cancers.
文摘Alzheimer's disease(AD) is a growing health problem. It has enormous public health impact. Sleep problems show an early component of this disease. Hypocretin hasa major function in sleep-wake cycle. The total number of hypocretin neurons in the normal humans ranges from 51000-83000, located exclusively in the hypothalamus. Deficiency in hypocretins neurotransmission results in narcolepsy, Parkinson's disease, and other neurological and psychological disorders. Cerebrospinal fluid(CSF) hypocretin levels were directly related with t-tau protein amount in AD. Increased hypocretin CSF in AD suggest that hypocretin is involved in the mechanism of AD pathology.
基金supported by the National Key Research and Development Program of China,Nos.2016YFC1306300(to XMW),2016YFC1306000the National Key R&D Program of China-European Commission Horizon 2020,No.2017YFE0118800-779238(to YXW)+15 种基金the Notional Natural Science Foundation of Chino,Nos.81970992(to WZ),81571229(to WZ),81071015(to WZ),30770745(to WZ)Capital's Funds for Health Improvement and Research(CFH),No.2022-2-2048(to WZ)the Key Technology R&D Program of Beijing Municipal Education Commission,No.kz201610025030(to WZ)the Natural Science Foundation of Beijing,No.7082032(to WZ)the Key Project of the Natural Science Foundation of Beijing,No.4161004(to WZ)Capitol Clinical Characteristic Applicotion Research,No.Z121107001012161(to WZ)Project of Scientific and Technological Development of Traditional Chinese Medicine in Beijing,No.JJ2018-48(to WZ)High Level Technical Personnel Training Project of Beijing Health System of China,No.2009-3-26(to WZ)Excellent Personnel Training Project of Beijing,No.20071D0300400076(to WZ)Important National Science&Technology Specific Project,No.2011ZX09102-003-01(to WZ)Beijing Healthcare Research Project,No.JING-15-2(to WZ)Basic-Clinicol Research Cooperation Funding of Capitol Medical University of China,Nos.2015-JL-PT-X04(to WZ),10JL49(to WZ),14JL15(to WZ)the Natural Science Foundation of Capital Medical UniversityBeijingChina,No.PYZ2018077(to PG)Youth Research Fund of Beijing Tianton Hospital of Capital Medical University of China,Nos.2015-YQN-14(to PG),2015-YQN-15,2015-YQN-17。
文摘Previous studies have shown that reduced sleep duration,sleep fragmentation,and decreased sleep quality in patients with Alzheimer's disease are related to dysfunction in orexin signaling.At the same time,blood-brain barrier disruption is considered an early biomarker of Alzheimer's disease.However,currently no report has examined how changes in orexin signaling relate to changes in the blood-brain barrier of patients who have Alzheimer's disease with sleep insufficiency.This cross-sectional study included 50 patients with Alzheimer's disease who received treatment in 2019 at Beijing Tiantan Hospital.Patients were divided into two groups:those with insufficient sleep(sleep duration≤6 hours,n=19,age 61.58±8.54 years,10 men)and those with normal sleep durations(sleep duration>6 hours,n=31,age 63.19±10.09 years,18 men).Demographic variables were collected to evaluate cognitive function,neuropsychiatric symptoms,and activities of daily living.The levels of orexin,its receptor proteins,and several blood-brain barrier factors were measured in cerebrospinal fluid.Sleep insufficiency was associated with impaired overall cognitive function that spanned multiple cognitive domains.Furthermore,levels of orexin and its receptors were upregulated in the cerebrospinal fluid,and the blood–brain barrier was destroyed.Both these events precipitated each other and accelerated the progression of Alzheimer's disease.These findings describe the clinical characteristics and potential mechanism underlying Alzheimer's disease accompanied by sleep deprivation.Inhibiting the upregulation of elements within the orexin system or preventing the breakdown of the blood-brain barrier could thus be targets for treating Alzheimer's disease.
