A newly discovered age-related synaptic change in the human locus ceruleus: morphometric and ultrastructural studies

We have recently found that in the human locus ceruleus (LC) some pigmented neurons contain granules in their cytoplasm that are immunoreactive (IR) for 38-kDa synaptic vesicle-specific protein (SVP). These represent synaptic terminals enveloped in the somatic cytoplasm. In the present study we analyzed LC pigmented neurons morphometrically in 48 autopsied individuals, whose ages at death ranged from 5 to 94 years, and also examined LC pigmented neurons ultrastructurally in 4 of these individuals. The number and incidence of LC pigmented neurons containing SVP-IR intracytoplasmic granules became significantly higher with age. The mean somatic area of the neurons was significantly higher than that of neurons without SVP-IR intracytoplasmic granules. Ultrastructurally, the synaptic terminals, which contained many round or flattened clear vesicles and sometimes dense-cored vesicles, were found to be enveloped by the somatic cytoplasm of some pigmented neurons and occasionally formed synaptic contacts with the cytoplasm. These enveloped synaptic terminals showed no apparent degenerative features. Our results strongly suggest that the enveloping of synaptic terminals by the somatic cytoplasm of human LC pigmented neurons is a phenomenon associated with the aging brain, and that this phenomenon may be related to intrinsic adaptive mechanisms of the LC pigmented neurons to certain environmental changes associated with aging.