Orexin neuronal changes in the locus coeruleus of the aging rhesus macaque

Jodi L. Downs, Michael R. Dunn, Erzsebet Borok, Marya Shanabrough, Tamas L. Horvath, Steven Kohama, Henryk Urbanski

    Research output: Contribution to journalArticle

    55 Citations (Scopus)

    Abstract

    Orexin neuropeptides regulate arousal state and excite the noradrenergic locus coeruleus (LC), so it is plausible that an age-related loss of orexin neurons and projections to the LC contributes to poor sleep quality in elderly humans and nonhuman primates. To test this hypothesis we examined orexin B-immunoreactivity in the lateral hypothalamic area (LHA) and the LC of male rhesus macaques (Macaca mulatta) throughout the life span. Orexin perikarya, localized predominantly in the LHA, showed identical distribution patterns irrespective of age. Similarly, orexin neuron number and serum orexin B concentrations did not differ with age. In contrast, orexin B-immunoreactive axon density in the LC of old animals was significantly lower than that observed in the young or adult animals. Furthermore, the age-related decline was associated with a significant decrease in tyrosine hydroxylase (TH) mRNA in the LC, despite no change in TH-immunoreactive neuron number. Taken together, these data suggest that age-related decreases in excitatory orexin innervation to the noradrenergic LC may contribute to the etiology of poor sleep quality in the elderly.

    Original languageEnglish (US)
    Pages (from-to)1286-1295
    Number of pages10
    JournalNeurobiology of Aging
    Volume28
    Issue number8
    DOIs
    StatePublished - Aug 2007

    Fingerprint

    Locus Coeruleus
    Macaca mulatta
    Lateral Hypothalamic Area
    Tyrosine 3-Monooxygenase
    Neurons
    Sleep
    Arousal
    Neuropeptides
    Primates
    Axons
    Young Adult
    Messenger RNA
    Serum
    Orexins

    Keywords

    • Aging
    • Axon density
    • Hypocretin
    • Lateral hypothalamic area (LHA)
    • Locus coeruleus (LC)
    • Orexin
    • Primate
    • Rhesus macaque
    • Tyrosine hydroxylase

    ASJC Scopus subject areas

    • Clinical Neurology
    • Biological Psychiatry
    • Developmental Neuroscience
    • Neurology
    • Psychology(all)

    Cite this

    Downs, J. L., Dunn, M. R., Borok, E., Shanabrough, M., Horvath, T. L., Kohama, S., & Urbanski, H. (2007). Orexin neuronal changes in the locus coeruleus of the aging rhesus macaque. Neurobiology of Aging, 28(8), 1286-1295. https://doi.org/10.1016/j.neurobiolaging.2006.05.025

    Orexin neuronal changes in the locus coeruleus of the aging rhesus macaque. / Downs, Jodi L.; Dunn, Michael R.; Borok, Erzsebet; Shanabrough, Marya; Horvath, Tamas L.; Kohama, Steven; Urbanski, Henryk.

    In: Neurobiology of Aging, Vol. 28, No. 8, 08.2007, p. 1286-1295.

    Research output: Contribution to journalArticle

    Downs, JL, Dunn, MR, Borok, E, Shanabrough, M, Horvath, TL, Kohama, S & Urbanski, H 2007, 'Orexin neuronal changes in the locus coeruleus of the aging rhesus macaque', Neurobiology of Aging, vol. 28, no. 8, pp. 1286-1295. https://doi.org/10.1016/j.neurobiolaging.2006.05.025
    Downs JL, Dunn MR, Borok E, Shanabrough M, Horvath TL, Kohama S et al. Orexin neuronal changes in the locus coeruleus of the aging rhesus macaque. Neurobiology of Aging. 2007 Aug;28(8):1286-1295. https://doi.org/10.1016/j.neurobiolaging.2006.05.025
    Downs, Jodi L. ; Dunn, Michael R. ; Borok, Erzsebet ; Shanabrough, Marya ; Horvath, Tamas L. ; Kohama, Steven ; Urbanski, Henryk. / Orexin neuronal changes in the locus coeruleus of the aging rhesus macaque. In: Neurobiology of Aging. 2007 ; Vol. 28, No. 8. pp. 1286-1295.
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