Browsing by Subject "GABA"

Histamine is an important neurotransmitter in the central nervous system (CNS). It is involved e.g. in the sleep-wake cycle, endocrine and energy homeostasis as well as in synaptic plasticity and learning. It is produced from L-histidine by histidine decarboxylase (HDC). Almost all species have histamine in their body although the amount varies between species. Histaminergic neurons are located in the tuberomamillary nucleus (TMN) of the posterior hypothalamus. There are four different histamine receptors in mammals and they are all metabotropic GPCR receptors. The first three (Hrh1, Hrh2 and Hrh3) are located in the brain while Hrh1 and Hrh2 along with Hrh4 that is mainly found in mast cells, are found in the periphery. Receptors have different functions e.g. Hrh1 regulates wakefulness and alertness while Hrh2 is involved in learning and memory. It is established that histaminergic neurons contain GABA-producing enzyme GAD1 and GABA itself. In the present study we aimed to evaluate GABAergic phenotype of the hypothalamic histaminergic neurons with double fluorescent in situ hybridization. Specifically, we were interested in co-existence of VGAT, which is responsible for vesicular release of GABA, and HDC mRNA. The animals used in this study were mouse and zebrafish. The percentage of mouse HDC-neurons that expressed GAD1 was 99.65% and co-expression for VGAT was also high (94.53%). This coexistence was verified also in the zebrafish model. Our data suggest that histaminergic neurons containing VGAT mRNA and are potentially able to release GABA. If GABA is released in a paracrine manner like histamine, it causes tonic inhibition that counterbalances the effects of histamine during wakefulness. The fact that VGAT mRNA was also found in zebrafish histaminergic neurons indicates that histamine-GABA system is preserved among species.