Changes in orexin (hypocretin) neuronal expression with normal aging in the human hypothalamus

Nicholas J. Hunt, Michael L. Rodriguez, Karen A. Waters, Rita Machaalani*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)292-300
Number of pages9
JournalNeurobiology of Aging
Issue number1
Publication statusPublished - 1 Jan 2015
Externally publishedYes


  • Adult
  • Brain
  • Development
  • Immunohistochemistry
  • Infant
  • Sleep


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