TY  - GEN
Y1  - 2013///
TI  - Characterisation of transcriptome changes caused by alcohol addiction
KW  - Alcoholism
KW  -  circadian rhythm
KW  -  impulsivity
KW  -  gene expression
KW  -  DNA microarray
ID  - heidok15964
A1  - Stählin, Oliver
N2  - Alcoholism is a psychiatric disorder whose main symptom is an uncontrollable desire to consume alcoholic beverages and which is often associated with a disturbed impulse control. The aim of this thesis was to improve the understanding of the molecular foundations of alcohol addiction and impulsive behaviour through four gene expression studies. The first sub-project analysed if there is an interaction between alcohol addiction and the body's 'endogenous clock'. DNA microarrays were used to measure genome-wide transcription rates in the nucleus accumbens of alcohol-drinking rats and control animals at different times of the day. The experiment did not provide evidence that such a systematic interaction is taking place in the investigated brain region. Based on the vast number of genes that were found to be diurnally oscillating, the study could nonetheless show how important it is to consider the time of measurement as an important variable in gene expression experiments. The second sub-project aimed at registering genome-wide transcription curves over a period of 24 hours in the blood of healthy human volunteers. Using also DNA microarrays, the main focus was again on genes with circadian oscillating expression levels. The obtained rhythmic expression profiles were mostly from immune genes and can now be used as a baseline for a follow-up study which will assess the impact of alcohol addiction on diurnal gene expression profiles in human blood. In the third study we analysed genome-wide transcription levels in the infralimbic cortex and the nucleus accumbens of rats which had been selectively bred for extremes of high and low impulsivity. This microarray study discovered several genes which were closely linked to the degree of impulsive behaviour in the rats. Some of the most differentially expressed genes were P2ry12, Frzb and Gprc5b. In the fourth sub-project we analysed the expression of four candidate genes,  AUTS2, GRIN3A, RASGRF2 and TACR1 in brain tissue taken from deceased alcoholics and non-alcoholic control persons. The expression of AUTS2 was linked to a single-nucleotide polymorphism (SNP) which was situated in an intronic region of the gene and which had been previously associated with increased alcohol consumption. No such link could be established for RASGRF2 concerning a similarly situated SNP. The expression of GRIN3A was elevated in the prefrontal cortex and the expression of TACR1 diminished in the anterior cingulate cortex of alcohol addicted subjects.
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/15964/
AV  - public
ER  -