title: CSF levels of hypocretin-1 (orexin-A) peak during early infancy in humans.
abstract: OBJECTIVE
  Hypocretin (orexin) is a unique neuropeptide involved in the consolidation of wakefulness and sleep. Although hypocretin-1 levels in the cerebrospinal fluid (CSF) are stable after infancy, how levels change in preterm and term human infants is unknown.
  
  
  METHODS
  Hypocretin-1 levels were measured in CSF samples, obtained from 284 preterm (25-37 gestational weeks) and full-term infants in the first 4 months of life and 35 older children (ages 0.5-13 years), in a tertiary hospital.
  
  
  RESULTS
  Detailed clinical and laboratory data were collected for each of the 319 participants. Based on that data, 108 neurologically intact children were selected (95 infants [43 preterm and 52 term] and 13 older children). CSF hypocretin-1 was measured by direct radioimmunoassay. Hypocretin-1 levels at the first weeks of the 3rd embryonic trimester (gestational age [GA] 28-34 weeks) were 314 ± 65 pg/mL (n = 17). The levels linearly increased during the third trimester and early infancy (r = 0.6), peaking in infants of 2-4 months ages (476 ± 72 pg/mL; n = 16) and decreasing thereafter; hypocretin levels in 2- to 4-month-old infants were significantly higher than those in children 0.5-13 years old (353 ± 78 pg/mL, n = 13; P = 0.0001).
  
  
  CONCLUSIONS
  The present findings indicate that in human infants, CSF hypocretin-1 increases during the third embryonic trimester and is highest at 4 months of life. Thereafter, and consistent with previously published results, hypocretin levels are lower and stable until the geriatric age. This pattern may reflect the role of hypocretin in the dramatic process of sleep and wakefulness consolidation that occurs during early infancy.
authors.affiliation: Neuropediatric Unit, Shaare Zedek Medical Center, Hebrew University, Jerusalem, Israel. aaran@szmc.org.il
authors.forename: Adi
authors.initials: A
authors.lastname: Aran
authors.forename: Irina
authors.initials: I
authors.lastname: Shors
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mignot
authors.forename: Michael S
authors.initials: MS
authors.lastname: Schimmel
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn / Q000134:cerebrospinal fluid*; D007234:Infant, Premature / Q000134:cerebrospinal fluid*; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid*; D009479:Neuropeptides / Q000134:cerebrospinal fluid*; D000068797:Orexins; D011863:Radioimmunoassay / Q000379:methods
chemical_list: C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins