Localization of tachykinins and their receptormRNAs in the human hypothalamus and basal forebrain

Abstract

Numerous studies in experimental animals have emphasized the importance of tachykinin peptides in hypothalamic function. There is however, little information on the location of these peptides in the human brain. In the first study, in situ hybridization was used to map the distribution of neurons expressing the substance P (SP) or neurokinin B (NKB) gene transcripts. The distribution of neurons containing tachykinin mRNAs was found to be distinct and complementary: SP was the predominant tachykinin in the striatum, posterior hypothalamus and intermediate, ventromedial and mammillary nuclei; there were more NKB mRNA containing neurons than SP neurons in the magnocellular basal forebrain, the bed nucleus, and the preoptic/anterior hypothalamic regions. Comparable numbers of neurons expressing both mRNAs were identified in the infundibular nucleus and amygdala. Because numerous neurons containing NKB mRNAs were identified in the nucleus basalis of Meynert, it was next determined if NKB mRNA and choline acetyltransferase (ChAT) mRNAs are colocalized in this region. It was found that approximately 30% of the cholinergic neurons in the nucleus basalis also expressed NKB gene transcripts. This is the first identification of peptide colocalization in a significant population of magnocellular cholinergic neurons in the human basal forebrain. The nucleus basalis of Meynert plays an important role in higher brain functions in humans. There is considerable evidence suggesting that SP and gonadotropin releasing hormone (GnRH) neurons are anatomically and functionally connected in the human brain. In this study, double in situ hybridization with 35S-labeled SP receptor (SPR) and digoxigenin-labeled GnRH riboprobes was used to determine if GnRH neurons contain SPR mRNAs. The radiolabeled GnRH riboprobe hybridized with scattered neurons in the preoptic-septal regions and medial basal hypothalamus. A digoxigenin-labeled GnRH probe labeled cells in the medial basal hypothalamus, the primate control center for reproduction. SPR mRNA was identified in numerous magnocellular basal forebrain neurons, however, GnRH neurons containing SPR mRNAs were not identified. Although the possibility that SPR mRNA may be present in these cells but below the level of detection remains, present data suggests that a link between SP and GnRH neurons does not exist in the human brain.