Age-related ultrastructural changes in hypocretinergic terminals in the brainstem and spinal cord of cats

In a previous study, we noted the presence of enlarged “spot-like” structures that are immunoreactive to hypocretin in specific regions of brainstem of aged cats; similar structures were not seen in the same regions of adult cats. In the present study, electron microscopy was combined with hypocretin immunohistochemistry to examine the ultrastructure of these enlarged “spot-like” structures, which were found to consist of enlarged axonal terminals. The terminals were comprised of a large pale core with a dark peripheral rim. Many granules were present within the core; most of these granular structures were not immunostained. On the other hand, the rim contained a high density of hypocretin immunoreactivity; in this peripheral region, large dense-core vesicles and small synaptic vesicles without dense cores were observed. In addition, mitochondria in the peripheral rim region exhibited high electron density, which is indicative of the presence of age-related degenerative changes. Synaptic contacts were observed between the enlarged terminals and adjacent dendrites. Most of these synapses were asymmetric (Gray type I), although a few of them were symmetric (Gray type II). These data suggest that hypocretin transmission is altered during aging, which would be expected to result in age-related changes in the functioning of the hypocretinergic system.