Dynorphin in pro-opiomelanocortin neurons of the hypothalamic arcuate nucleus

Abstract

Considerable evidence suggests that dynorphin participates in the regulation of energy balance. In this study, we have used immunohistochemistry to investigate in detail the cellular localization of pro-dynorphin (DYN) immunoreactive cell bodies in the mediobasal hypothalamus with special reference to neurons producing orexigenic or anorexigenic transmitters. In colchicine-treated rats, DYN immunoreactivity was demonstrated in many cell bodies of the arcuate nucleus (Arc). Double-labeling revealed that DYN immunoreactivity was present in approximately 30% of pro-opiomelanocortin (POMC) neurons in the ventrolateral Arc as shown by presence of α-melanocyte-stimulating hormone (α-MSH) and cocaine- and amphetamine-regulated transcript (CART). In contrast, DYN immunoreactivity was not demonstrated in agouti-related peptide (AgRP)- or neuropeptide Y (NPY) –containing neurons in the ventromedial aspect of the Arc. Dynorphin immunoreactivity was also colocalized with the vesicular acetylcholine (ACh) transporter (VAChT; a marker for cholinergic neurons) in the cell soma of Arc POMC neurons. Brainstem POMC neurons in the commissural part of the solitary tract nucleus (NTS) were devoid of DYN immunoreactivity, whereas DYN immunoreactivity was detected in a few NPY-containing NTS neurons and cholinergic DMX neurons. Our results showing presence of DYN together with α-MSH in a subpopulation of hypothalamic POMC neurons further point to the neurochemical heterogeneity of hypothalamic POMC neurons. The results suggest a role for DYN in control of energy balance by mediating the effect of peripheral hormones such as leptin and insulin.