Age-related changes in hypocretin (orexin) immunoreactivity in the cat brainstem

Terminals of hypothalamic hypocretin-containing neurons are observed within brainstem nuclei involved in the control of sleep and wakefulness. Because aged humans, cats and other species exhibit changes in sleep and wakefulness in old age, we were interested in examining age-related changes in hypocretin/orexin projections to the following brainstem regions which are associated with the regulation of sleep and wakefulness: the dorsal raphe nucleus, the laterodorsal tegmental nucleus, the pedunculo-pontine tegmental nucleus and the locus coeruleus. Based upon the results of immunohistochemical determinations, in all the regions examined, round or oval "spot-like" structures were observed in aged cats. Many of these "spot-like" structures resembled enlarged varicosities of a nature that would be expected to disrupt hypocretin neurotransmission. In addition, a site-specific decrease in immunostaining was observed in the locus coeruleus in old cats compared with adult controls; this result likely reflects a decrease in the number of labeled fibers, which indicates that there occurs a degeneration of hypocretinergic function in conjunction with old age. The proceeding changes may account for some of sleep-wake disturbance which are observed in aged animals as well as elderly humans.