Distinct features of neurotransmitter systems in the human brain with focus on the galanin system in locus coeruleus and dorsal raphe

Using riboprobe in situ hybridization, we studied the localization of the transcripts for the neuropeptide galanin and its receptors (GalR1-R3), tryptophan hydroxylase 2, tyrosine hydroxylase, and nitric oxide synthase as well as the three vesicular glutamate transporters (VGLUT 1-3) in the locus coeruleus (LC) and the dorsal raphe nucleus (DRN) regions of postmortem human brains. Quantitative real-time PCR (qPCR) was used also. Galanin and GalR3 mRNA were found in many noradrenergic LC neurons, and GalR3 overlapped with serotonin neurons in the DRN. The qPCR analysis at the LC level ranked the transcripts in the following order in the LC: galanin >> GalR3 >> GalR1 > GalR2; in the DRN the ranking was galanin >> GalR3 >> GalR1 = GalR2. In forebrain regions the ranking was GalR1 > galanin > GalR2. VGLUT1 and -2 were strongly expressed in the pontine nuclei but could not be detected in LC or serotonin neurons. VGLUT2 transcripts were found in very small, nonpigmented cells in the LC and in the lateral and dorsal aspects of the periaqueductal central gray. Nitric oxide synthase was not detected in serotonin neurons. These findings show distinct differences between the human brain and rodents, especially rat, in the distribution of the galanin system and some other transmitter systems. For example, GalR3 seems to be the important galanin receptor in both the human LC and DRN versus GalR1 and -2 in the rodent brain. Such knowledge may be important when considering therapeutic principles and drug development.