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

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.