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CSF levels of hypocretin-1 (orexin-A) peak during early infancy in humans
Adi Aran1, Irina Shors, Ling Lin
1Neuropediatric Unit, Shaare Zedek Medical Center, Hebrew University, Jerusalem, Israel. aaran@szmc.org.il
Insights
Cerebrospinal fluid hypocretin-1 levels increase during the third trimester and early infancy, peaking at 4 months. These levels then stabilize, reflecting hypocretin
Area of Science:
- Neuroscience
- Pediatrics
- Sleep Medicine
Background:
- Hypocretin (orexin) is a neuropeptide crucial for regulating wakefulness and sleep.
- Cerebrospinal fluid (CSF) hypocretin-1 levels are generally stable after infancy.
- Changes in CSF hypocretin-1 during early human development, particularly in preterm and term infants, remain largely uncharacterized.
Purpose of the Study:
- To investigate the developmental trajectory of CSF hypocretin-1 levels in human infants.
- To determine how hypocretin-1 levels change from the third embryonic trimester through early infancy.
- To compare hypocretin-1 levels in infants with those in older children.
Main Methods:
- CSF samples were collected from 284 preterm and full-term infants (first 4 months) and 35 older children (0.5-13 years).
- Hypocretin-1 levels were quantified using direct radioimmunoassay.
- Data analysis focused on 108 neurologically intact children, including 95 infants (43 preterm, 52 term).
Main Results:
- CSF hypocretin-1 levels at 28-34 weeks gestational age were 314 ± 65 pg/mL.
- Levels showed a linear increase (r = 0.6) during the third trimester and early infancy.
- Peak levels of 476 ± 72 pg/mL were observed in infants aged 2-4 months, significantly higher than in older children (353 ± 78 pg/mL; P = 0.0001).
Conclusions:
- CSF hypocretin-1 levels increase significantly during human fetal development and early infancy.
- Hypocretin-1 levels peak around 4 months of age and subsequently stabilize.
- This developmental pattern suggests a role for hypocretin in the consolidation of sleep-wake cycles during early life.
Study Objectives:
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.
Design, Patients, And Setting:
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.
Measurements And 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.
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