Dokument: Electrophysiological and molecular analysis of aminergic neurons controlling arousal
| Titel: | Electrophysiological and molecular analysis of aminergic neurons controlling arousal | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=8184 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20080703-083622-8 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | English, Middle (1100-1500) | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Klyuch, Boris [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Haas, Helmut L. [Gutachter] Prof. Dr. Rose, Christine R. [Gutachter] | |||||||
| Stichwörter: | Hypothalamus, histaminergic system, sleep, waking, modafinil, thyrotropin-releasing hormon, adenosine | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | One of the most important roles of histaminergic and dopaminergic systems is regulation of sleep-waking cycle (Brown et al., 2001). In my thesis I and colleagues showed the effect of several well-known wake (or sleep) - promoting neurotransmitters and substance on the activity of HAergic and DAergic neurons.
Adenosine does not change the firing rate or membrane potential of TMN neurons in hypothalamic brain slices (Sergeeva et al., 2006). These results support the idea about indirect modulation of HAergic systems with adenosine. In contrast, ATP, ADP and UTP excite TMN neurons in hypothalamic slices (Sergeeva et al., 2006). With a help of expression analysis we found that P2Y1 and P2Y4 receptors are the major target for purines in TMN neurons. The other point of this work is found interactions between TMN neurons and glial cells (Sergeeva et al., 2006). Our immunostaining revealed that metabotropic P2Y1 receptors are widely expressed both in neurons and nuclear of the glial cells. Moreover, the effect of ATP and ADP was reduced but was not eliminated completely by prior application of P2Y1 antagonist. According to this data we proposed that glial P2Y1 receptors are activated after uptake of nucleotides with followed increase of glutamate release (Sergeeva et al., 2006). In other work we showed that TRH increased the firing rate and induced membrane depolarization directly through TRH1 and TRH2 receptors (Parmentier et al., in preparation). On other hand, TRH mediates frequency but not amplitude of spontaneous inhibitory postsynaptic currents indicating indirect effect (Parmentier et al., in preparation). Modafinil is a novel wake-promoting drug but the mechanism of it action remains unclear. In our work we showed that modafinil does not change the activity of HAergic neurons and inhibit DAergic neurons from substantia nigra and ventral tegmental area. This action does not involve the adrenergic system, but is related to D2-like receptor activation. Considering our data, we suggest that D2-like receptors are the major if not unique target of modafinil in the DAergic neurons. All our findings are relevant for better understanding of the role of adenosine, ATP, TRH and modafinil as well HAergic and DAergic systems in the sleep-waking regulation. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Biologie | |||||||
| Dokument erstellt am: | 24.06.2008 | |||||||
| Dateien geändert am: | 24.06.2008 | |||||||
| Promotionsantrag am: | 14.05.2008 | |||||||
| Datum der Promotion: | 19.06.2008 |
