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

Neurobiol Aging. 2015 Jan;36(1):292-300. doi: 10.1016/j.neurobiolaging.2014.08.010. Epub 2014 Aug 13.

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.

Keywords: Adult; Brain; Development; Immunohistochemistry; Infant; Sleep.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging / genetics*
  • Aging / metabolism*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Hypothalamus / cytology*
  • Hypothalamus / metabolism*
  • Infant
  • Infant, Newborn
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Male
  • Middle Aged
  • Neurons / metabolism*
  • Neuropeptides / metabolism*
  • Neuropeptides / physiology*
  • Orexins
  • Sleep / genetics*
  • Sleep / physiology*
  • Young Adult

Substances

  • HCRT protein, human
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins