Differential distribution of corticotropin-releasing hormone immunoreactive axons in monoaminergic nuclei of the human brainstem

Abstract

Corticotropin-releasing hormone (CRH) has been implicated in a variety of physiological and behavioral responses to stress, as well as in the pathophysiology of certain psychiatric disorders. Although studies in rodents support a neuromodulatory influence of CRH on monoamine neurotransmission in a number of brain regions, little information in available to support a similar role for CRH in the human brain. The present study used immunocytochemistry to characterize the anatomical organization of CRH-immunoreactive axons in the human brainstem. Substantial regional differences in the density and distribution of CRH-immunoreactive axons were found in the dopamine-, noradrenaline- and serotonin-containing cell body regions of the human brainstem. Dense networks of CRH-immunoreactive axons were found in the medial subnuclei of the ventral mesencephalon and in the dorsolateral region of the locus coeruleus. Moderate densities of CRH-positive fibers were located in the median and dorsal raphe, whereas lower numbers of CRH-labeled axons appeared in the substantia nigra pars compacta. In addition, differences in CRH innervation density were observed within each region. For example, the dorsal tier of the substantia nigra contained a greater density of CRH-labeled axons than the ventral tier. In all monoamine-containing nuclei, CRH-labeled axons exhibited numerous beaded varicosities and fine intervaricose segments. The differential distribution of CRH-containing axons across these human brainstem nuclei suggests that the influence of CRH on monoamine function may be neurotransmitter-specific.