CAN:s bibliotek

*00001292nam 122003137a 4500
*00128894
*00520160510080113.0
*008160510s2016    sw ||||e m    00| ||eng c
*020  $a9789155495541
*035  $a(DiVA)urn:nbn:se:uu:diva-283065
*035  $a(SE-LIBR)19453912
*1001 $aTodkar, Aniruddha,$d1983-
*24510$aAlcohol consumption :$ba study of genetic and environmental correlates with focus on the stress system /$cAniruddha Todkar
*260  $aUppsala : $bActa Universitatis Upsaliensis,$c2016
*300  $a58 s.
*4901 $aDigital comprehensive summaries of Uppsala dissertations from the Faculty of Medicine,$x1651-6206 ;$v1214
*500  $aHärtill 4 uppsatser
*502  $aDiss. (sammanfattning) Uppsala : Uppsala universitet, 2016
*5208 $aEarly life stress (ELS) is associated with risk of excessive alcohol drinking. However, the genetic mechanisms underlying the susceptibility to excessive alcohol drinking are not well understood. DNA methylation may mediate the influence of ELS on gene function and thereby contribute to alcohol misuse. Furthermore, susceptible genotypes of polymorphisms in interaction with early environment may influence alcohol related behaviors in adulthood. The present thesis comprised of a study of rodents and a study of humans. The former aimed to investigate the effects of ELS, alcohol drinking and housing on the expression of stress and DNA methylation regulatory genes in the hypothalamus and pituitary, and the expression of the Fkbp5 in the mesocorticolimbic system and dorsal striatum. The effects of ELS, alcohol, and housing on the DNA methylation of the promoters of genes of interest and blood corticosterone levels were also examined. Hypothalamic Adra2a expression was lower in alcohol drinking rats exposed to ELS, whereas ELS and ethanol drinking exerted independent effects on the expression of other genes in the hypothalamus and pituitary, however in a manner that depended on the control group used. Single housing associated with differential gene expression suggesting single housing as a confounding factor. Water and ethanol drinking in rats exposed to ELS was associated with higher and lower blood corticosterone, respectively. Brain region-dependent interaction effects between alcohol and ELS were observed on Fkbp5 expression in mesolimbic regions. These results indicate a counter-balancing effect of alcohol drinking to ELS. Altogether, the present thesis deepens the knowledge of underlying genetic mechanisms for ELS-mediated propensity to drink alcohol and presents the novel insight into genetic susceptibility of FKBP5 and CRHR1 to early environment in relation to alcohol drinking problems. (From the abstract)
*650 4$aAlcohol drinking
*650 4$aStress, psychological
*650 4$aGene expression
*650 4$aAnimals, laboratory
*653  $aStress
*653  $aseparation
*653  $aAlkoholkonsumtion
*830 0$aDigital comprehensive summaries of Uppsala dissertations from the Faculty of Medicine, $x1651-6206 ; $v1214 $0362750 $0372309
*852  $hDiss.500
*85642$uhttp://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-283065
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