Depletion of ventromedullary NK-1, receptor-immunoreactive neurons in multiple system atrophy

Abstract

We sought to determine whether there are neurokinin-1 receptor-like-immunoreactive (NK-1R-LI) neurons in human ventrolateral medulla and whether these neurons are more severely involved in multiple system atrophy (MSA) than in Parkinson's disease. Brains were obtained at autopsy from six control subjects, six subjects with clinical diagnosis of MSA and four with Parkinson's disease, both confirmed neuropathologically. Serial 50 μm cryostat sections were obtained throughout the medulla, and every eighth section was processed for NK-1R-LI neurons. Some sections were processed simultaneously for tyrosine hydroxylase or choline acetyltransferase. Abundant NK-1R-LI neurons were identified in the ventrolateral medulla. These neurons were distinct from local cholinergic or catecholaminergic neurons. There was a severe depletion of these NK-1R-LI neurons in all MSA cases compared with controls (6 ± 1 cells/section versus 49 ± 2 cells/section in controls). Although there was also a reduction in Parkinson's disease (20 ± 2 cells/section), this was significantly less severe than in MSA. Our findings suggest that the human ventrolateral medulla contains NK-1R-LI neurons, and the more severe depletion in MSA than in Parkinson's disease may explain the higher incidence of respiratory and cardiovascular abnormalities in the former condition.