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

We sought to determine whether the putative pontine micturition center in t he human dorsal pons contains corticotrophin-releasing factor (CRF) neurons , and whether these neurons are depleted in patients with multiple system a trophy and bladder dysfunction. Brains were obtained at autopsy from 4 cont rol subjects and 4 patients with clinical diagnosis of multiple system atro phy, confirmed neuropathologically. Serial 50 mum cryostat sections were ob tained throughout the rostral half of the pons, and every eighth section wa s processed for CRF immunocytochemistry (rabbit polyclonal antibody). Conse cutive sections were stained for nicotinamide adenine dinucleotide phosphat e diaphorase (NADPH-d) to identify neurons of the laterodorsal tegmental nu cleus or for both CRF and NADPH. Locus ceruleus neurons were identified by their neuromelanin content. Abundant CRF immunoreactive neurons were identi fied in the dorsal pontine tegmentum just ventral to the locus. ceruleus. C RF neurons were intermingled with, but distinct from, the NADPH-d reactive neurons of the laterodorsal tegmental nucleus. In all multiple system atrop hy cases, there was a severe depletion of these CRF-immunoreactive neurons (26.6 +/- 3 neurons/section in patients; 73.7 +/- 4 neurons/section in cont rols). Our results suggest that depletion of CRF neurons in the putative po ntine micturition center may contribute to the severe bladder dysfunction t hat characterizes multiple system atrophy.