Post-mortem brains of alcoholics: changes in the glutamatergic, serotonergic, endocannabinoid and neuroactive steroid systems
Year: 2016
Type: dissertation
Study design: Observational Study
Abstract: Alcohol (ethanol) consumption is one of the leading risk factors for many serious diseases.The pharmacology of ethanol is extremely complex, affecting many of the signaling systems not only in the brain but widely throughout the body.Alcoholics are a heterogeneous group of subjects suffering a wide spectrum of problems.Cloninger's typology divides the spectrum of alcoholics into two subgroups: anxiety-prone late onset type 1 alcoholics and early onset, impulsive and antisocial type 2 alcoholics.Here the post-mortem brain samples of Cloninger type 1 (N=9) and type 2 (N=8) alcoholics have been studied and compared to non-alcoholic controls (N=10).The first sub-study evaluated [ 3 H]AMPA binding to AMPA receptors.Increased binding was observed in the anterior cingulate cortex of type 2 alcoholics in comparison with controls.This elevated [ 3 H]AMPA binding could be associated with increased impulsivity in these individuals.The second study investigated the endocannabinoid levels in the post-mortem samples of hippocampus and amygdala.Increased docosahexaenoylethanolamide levels were observed in late-onset type 1 alcoholics in the amygdala.Furthermore, a negative correlation was observed between anandamide levels and previously published metabotropic glutamate receptor 1/5 levels in the hippocampus in type 1 alcoholics, but not in controls or type 2 alcoholics.These observations could be associated with the transient receptor potential vanilloid type 1 mediated synaptic plasticity which is dependent on metabotropic glutamate receptor 5 and anandamide function.In the third study, [ 3 H]citalopram binding to serotonin transporters was measured in brain regions associated with social cognition.Decreased [ 3 H]citalopram binding was observed in the posterior cingulate cortex and posterior insula in all alcoholics when compared to nonalcoholic controls.Furthermore, decreased [ 3 H]citalopram binding in the parahippocampal gyrus was seen only in the antisocial type 2 alcoholics.The decreased serotonin transporter binding in alcoholics could be associated with altered social cognitive processes.The fourth study examined levels of neuroactive steroids in the post-mortem brain samples.Increased dehydroepiandrosterone levels were seen in all alcoholics compared to controls.There were also negative correlations detected between pregnenolone levels and the previously published [ 3 H]naloxone binding to μ-opioid receptors and similarly, increased pregnenolone levels were observed only in a sub-group of alcoholics with decreased [ 3 H]naloxone binding in comparison with the controls.Overall, the findings of the present thesis improve our understanding of the differences between the brains of alcoholics and controls.Furthermore, they highlight the need to recognize the spectrum of alcoholics in research which hopefully will be translated into improvements in the treatment of alcoholism.
Author: Kärkkäinen, Olli
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3096472609