DARWIN Digitale Dissertationen German Version Strich

FU Berlin
Digitale Dissertation

Oliver Brödel :
Quantification of thyroid hormones in subcellular fractions of different areas of rat brain
effects of antidepressant drugs, of stress and of hypo- and hyperthyroidism
Quantifizierung von Schilddrüsenhormonen in subzellulären Fraktionen verschiedener Areale des Rattenhirns

FU Logo

|Abstract| |Table of Contents| |More Information|


Thyroid hormones exert their physiological actions at specific subcellular structures. However, in rat brain, the concentrations of iodothyronines have to date been measured in homogenates of brain regions only. Therefore, in the present study a method is developed for fractionating the tissue of 11 areas of the rat brain by sucrose density centrifugation into five subcellular fractions: nuclei, mitochondria, myelin, synaptosomes and microsomes. The purity of each fraction was evaluated by quantification of biochemical "markers" and electron microscopy. The thyroid hormones T3 and T4 were quantified in these fractions using sensitive radioimmunoassays. Miscellaneous pharmacological and non-pharmacological treatments showed the following results: a) four chemically different antidepressive drugs induced an increase of the concentrations of T3 in the myelin fraction of the amygdala. The mood stabilizers lithium and carbamazepine as well as an 8 hours' partial sleep deprivation enhanced the levels of T3 in the synaptosomes in the amygdala. Antidepressants also induced an increase of the mitochondrial protein concentrations and the activity of the mitochondrial enzyme succinate dehydrogenase in the amygdala. The results show that these psychiatric drugs by means of their effects on the thyroid hormone concentrations affect specific amygdaloid functions. These effects are involved likely in the as yet unknown mechanisms of action of these therapies. b) Different kinds of stress, e.g. acute or over a period of 14 days executed i.p. injections of isotonic sodium chlorid, led to specific changes of the T3 concentratios in different subcellular fractions. c) The induction of a hyperthyroidism with T3 or with T4 induced an increase of the T3 tissue concentrations only in one of four brain areas, in the other three areas the T3 concentrations remained unchanged on account of counterregulative mechanisms. In conclusion, the present study shows that through the measurement of thyroid hormones in subcellular fractions pharmacological effects can be discovered which are overlooked if the hormones are quantified solely in homogenates. The most important partial results are the clear indications of the effects of different antidepressant drugs and mood stabilizers in subcellular structures of the amygdala.

Table of Contents

Download the whole PhDthesis as a zip-tar file or as zip-File

For download in PDF format click the chapter title

1. Titel und ausführliches Inhaltsverzeichnis
1. Einleitung 1
2. Material und Methoden 26
3. Ergebnisse 59
4. Diskussion 99
5. Literaturverzeichnis 120
6. Publikationsliste 136

More Information:

Online available: http://www.diss.fu-berlin.de/2002/254/indexe.html
Language of PhDThesis: german
Keywords: subcellular fractionation, thyroid hormones, antidepressants, rat brain
DNB-Sachgruppe: 33 Medizin
Date of disputation: 08-Oct-2002
PhDThesis from: Fachbereich Humanmedizin, Freie Universität Berlin
First Referee: Prof. Dr. Andreas Baumgartner
Second Referee: Prof. Dr. Hans Rommelspacher
Contact (Author): Broedelukbf@aol.com
Date created:25-Nov-2002
Date available:04-Dec-2002


|| DARWIN|| Digitale Dissertationen || Dissertation|| German Version|| FU Berlin|| Seitenanfang ||

Mail-Icon Fragen und Kommentare an:

© Freie Universität Berlin 1999