Depletion of corticotrophin-releasing factor neurons in the pontine micturition area in multiple system atrophy

Abstract

We sought to determine whether the putative pontine micturition center in the human dorsal pons contains corticotrophin-releasing factor (CRF) neurons, and whether these neurons are depleted in patients with multiple system atrophy and bladder dysfunction. Brains were obtained at autopsy from 4 control subjects and 4 patients with clinical diagnosis of multiple system atrophy, confirmed neuropathologically. Serial 50μm cryostat sections were obtained throughout the rostral half of the pons, and every eighth section was processed for CRF immunocytochemistry (rabbit polyclonal antibody). Consecutive sections were stained for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) to identify neurons of the laterodorsal tegmental nucleus or for both CRF and NADPH. Locus ceruleus neurons were identified by their neuromelanin content. Abundant CRF immunoreactive neurons were identified in the dorsal pontine tegmentum just ventral to the locus ceruleus. CRF neurons were intermingled with, but distinct from, the NADPH-d-reactive neurons of the laterodorsal tegmental nucleus. In all multiple system atrophy cases, there was a severe depletion of these CRF-immunoreactive neurons (26.6 ± 3 neurons/section in patients; 73.7 ± 4 neurons/section in controls). Our results suggest that depletion of CRF neurons in the putative pontine micturition center may contribute to the severe bladder dysfunction that characterizes multiple system atrophy.