Browsing by Subject "Brain"
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(2018)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.
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(2023)The histamine system in the brain has many important functions, including regulating the sleep-wake cycle, locomotor activity, cognition and memory. Gamma-Aminobutyric acid (GABA) on the other hand is the most important inhibitory transmitter in the brain, thus important for example in inducing sleep. Disturbances in these systems are present in various neurological diseases. Of the various histamine receptors, the histamine receptor 3 (HRH3) has a unique role in restricting the synthesis and release of both histamine and other transmitters, including glutamate, acetylcholine, dopamine and noradrenaline. GABA is synthesized from glutamic acid by glutamic acid decarboxylase (GAD), which has two different isoforms, GAD65 and GAD67. NKCC1 and KCC2 are ion transporter molecules essential for the development of the GABA system. The aim of this study was to examine the effect the HRH3 has on four essential genes regarding the GABAergic system GAD65, GAD67, KCC2, and NKCC1. This was accomplished using a HRH3 knockout zebrafish strain. The expression patterns of the genes were visualized by whole-mount in situ hybridization. The GAD67 and KCC2 gene expression patterns were also visualized in zebrafish brains treated with HRH3 antagonists ciproxifan and thioperamide. The results of the study showed that knocking out of the HRH3 did not seem to have an effect on the expression of the studied GABAergic genes. Samples treated with thioperamide or ciproxifan on the other hand showed diminished gene expression. This indicates that these pharmaceutical agents decrease the expression of KCC2, revealing new information about their effect on brain function. This result still needs to be confirmed using quantitative methods. New information about the genes was also acquired regarding their expression in the wild type zebrafish. For GAD65 and GAD67 new information was gained about the changes in expression during the zebrafish development. For KCC2 and NKCC1 the expression patterns in the zebrafish brain are completely new, previously unpublished information.
Now showing items 1-2 of 2