HCRT
Orexin precursor (Hypocretin) (Hcrt) [Contains: Orexin-A (Hypocretin-1) (Hcrt1); Orexin-B (Hypocretin-2) (Hcrt2)] [OX] [PPORX] [PPOX]
Publications[править]
Orexin A (OXA) and neuropeptide Y (NPY) are two hypothalamic neuropeptides involved in the regulation of feeding behavior and food intake in all vertebrates. Accumulating evidences document that they undergo age-related modifications, with consequences on metabolism, sleep/wake disorders and progression of neurodegenerations. The present study addressed the age related changes in expression and distribution of orexin A (its precursor is also known as hypocretin-HCRT) and NPY, and their regulation by food intake in the short-lived vertebrate model Nothobranchius furzeri. Our experiments, conducted on male specimens, show that: (a) HCRT and OXA and NPY mRNA and protein are localized in neurons of diencephalon and optic tectum, as well as in numerous fibers projecting through the entire neuroaxis, and are colocalized in specific nuclei; (b) in course of aging, HCRT and NPY expressing neurons are localized also in telencephalon and rhombencephalon; (c) HCRT expressing neurons increased slightly in the diencephalic area of old animals and in fasted animals, whereas NPY increased sharply; (d) central HCRT levels are not regulated neither in course of aging nor by food intake; and (e) central NPY levels are augmented in course of aging, and regulated by food intake only in young. These findings represent a great novelty in the study of central orexinergic and NPY-ergic systems in vertebrates', demonstrating an uncommon and unprecedented described regulation of these two orexigenic neuropeptides.
MeSH Terms
- Aging
- Amino Acid Sequence
- Animals
- Conserved Sequence
- Diencephalon
- Eating
- Fasting
- Fundulidae
- Gene Expression Regulation
- Hypothalamus
- In Situ Hybridization
- Male
- Neurons
- Neuropeptide Y
- Orexins
- Sequence Alignment
- Sequence Homology, Amino Acid
- Superior Colliculi
Keywords
HCRT
- NPY
- RRID:AB_1566510
- RRID:AB_653610
- RRID:AB_91545
- aging
- food intake
- hypothalamus
- teleost fish
Narcolepsy with cataplexy (NC) is a lifelong disorder caused by loss of hypothalamic hypocretin/orexin (HCRT) neurones, often starting in childhood. NC patients show altered control of heart rate (HR) and a normotensive non-dipper blood pressure (BP) profile, but the natural history and prognostic significance of these alterations remain unclear. Similar alterations have been observed in HCRT-ataxin-3 transgenic (TG) NC mice lacking HCRT neurones, but studies have been limited to young adult individuals <4 months of age. Here we evaluated long-term effects of NC on derangements in the wake-sleep state and cardiovascular control by studying middle-aged TG. We chronically instrumented TG and wild-type mice aged 10-11 months with electrodes for sleep scoring and a telemetric transducer for BP and HR measurements. We then recorded mice in freely behaving conditions. TG showed a NC phenotype including fragmentation of wakefulness, reduced latency to rapid eye movement sleep (REMS) and cataplexy-like events. TG also showed blunted BP decline on entering non-rapid eye movement sleep (NREMS), enhanced BP increase on passing to REMS, increased HR, and blunted changes in HR upon arousal and awakening from NREMS. Histological and ultrastructural analysis of cardiovascular and renal tissue did not reveal evidence of subclinical hypertensive organ damage. These data indicate that HCRT neurone loss in TG causes alterations in wake-sleep behaviour and cardiovascular control that are not peculiar to the beginning of the disease but are maintained at least up to middle age. These alterations are similar to those in adult NC patients, but do not produce early subclinical damage to the heart and kidneys.
MeSH Terms
- Aging
- Animals
- Blood Pressure
- Body Weight
- Cataplexy
- Heart Rate
- Intracellular Signaling Peptides and Proteins
- Male
- Mice
- Neurons
- Neuropeptides
- Orexins
- Phenotype
- Sleep
- Sleep, REM
- Wakefulness
Keywords
- ageing
- arterial blood pressure
- heart rate
- kidney
- narcolepsy
- orexin