title: Changes in orexin (hypocretin) neuronal expression with normal aging in the human hypothalamus.
abstract: Animal studies have shown that decreased orexin expression changes sleep regulation with normal aging. This study examined orexin A and B expression in the tuberal hypothalamus in infants (0-1 year; n = 8), children (4-10 years; n = 7), young adults (22-32 years; n = 4), and older (48-60 years; n = 7) adults. Neuronal expression was defined by the percentage positive orexin immunoreactive (Ox-ir) neurons in the whole tuberal hypothalamus, and in the dorsal medial (DMH), perifornical, and lateral hypothalamus. In addition, the number of Ox-ir neurons/mm(2), regional distribution, and co-localization were examined. Within the whole tuberal hypothalamic section, there was a 23% decrease in the percentage of Ox-ir neurons between infants and older adults (p < 0.001), and a 10% decrease in older compared with younger adults (p = 0.023). These changes were confined to the DMH and/or perifornical hypothalamus. There was a 9%-24% decrease in Ox neurons/mm(2) in adults compared with infants and/or children (p ≤ 0.001). These results demonstrate a decrease in Ox expression with normal human maturation and aging. This may contribute to changes in sleep regulation during development and with aging.
authors.affiliation: Department of Medicine, Central Clinical School, University of Sydney, New South Wales, Australia; SIDS and Sleep Apnea Laboratory, BOSCH Institute of Biomedical Research, University of Sydney, New South Wales, Australia.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Hunt
authors.affiliation: Department of Forensic Medicine, NSW Forensic and Analytical Science Service, Glebe, New South Wales, Australia.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Rodriguez
authors.affiliation: Department of Medicine, Central Clinical School, University of Sydney, New South Wales, Australia; SIDS and Sleep Apnea Laboratory, BOSCH Institute of Biomedical Research, University of Sydney, New South Wales, Australia; SIDS and Sleep Apnea Laboratory, The Children's Hospital, Westmead, New South Wales, Australia.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Waters
authors.affiliation: Department of Medicine, Central Clinical School, University of Sydney, New South Wales, Australia; SIDS and Sleep Apnea Laboratory, BOSCH Institute of Biomedical Research, University of Sydney, New South Wales, Australia; SIDS and Sleep Apnea Laboratory, The Children's Hospital, Westmead, New South Wales, Australia. Electronic address: ritam@med.usyd.edu.au.
authors.forename: Rita
authors.initials: R
authors.lastname: Machaalani
mesh_terms: D000328:Adult; D000375:Aging / Q000235:genetics* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000166:cytology* / Q000378:metabolism*; D007223:Infant; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism* / Q000502:physiology*; D000068797:Orexins; D012890:Sleep / Q000235:genetics* / Q000502:physiology*; D055815:Young Adult
chemical_list: C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins
keywords: Adult; Brain; Development; Immunohistochemistry; Infant; Sleep