| dc.contributor.advisor | Fischer, André Prof. Dr. | |
| dc.contributor.author | Löns, Sebastian | |
| dc.date.accessioned | 2015-10-07T09:09:55Z | |
| dc.date.available | 2015-10-20T22:50:06Z | |
| dc.date.issued | 2015-10-07 | |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-0023-963D-C | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-5296 | |
| dc.language.iso | deu | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 610 | de |
| dc.title | Epigenetik in der Schizophrenie und der Einfluss von Histon-Deacetylasen auf die Arbeitsgedächtnisfunktion | de |
| dc.type | doctoralThesis | de |
| dc.title.translated | Epigenetics in schizophrenia and the influence of histone deacetylases on working memory | de |
| dc.contributor.referee | Wirths, Oliver Pd Dr. | |
| dc.date.examination | 2015-10-13 | |
| dc.description.abstracteng | Schizophrenia is a chronic disease leading to impairment in social and occupational functioning.
The etiology remains elusive. Current concepts presume a genetic susceptibility, which
in combination with environmental stimuli leads to the clinical manifestation. Cognitive dysfunction,
especially deficits in working memory are regarded core deficits in schizophrenia.
Working memory function is thought to be located in the prefrontal cortex. Epigenetics in
a neuroscientific definition describes the mechanisms in which external stimuli change gene
expression in postmitotic brain cells. The mechanisms of histone acetylation and DNA methylation
are especially well characterized. It is known, that the formation of long-term memory
involves epigenetic processes. The present thesis deals with the question, whether epigenetic
mechanisms also regulate working memory processes.
Postmortal brain samples from the dorsolateral PFC showed significant hyperacetylation
at histone 4 in schizophrenics and overexpression of hdac1 while other nuclear HDAC were
normally expressed. Determination of working memory-related receptors showed a reduction
of muscarinic acetylcholine-receptor 1 (ChRM1) and of AMPA glutamate receptor, subunit
1 (GluR1) in schizophrenics. Investigation of epigenetic processes showed a hypomethylation
of the chrm1-promotor region. To further determine the epigenetic influence on working
memory processes in a prospective manner we examined the effect of the histone deacetylase
inhibitors (HDACi) sodiumbutyrate and phenylbutyrate in a methionine-induced mouse model
for schizophrenia. Chronic application of intraperitoneal methionine did not result in reduced
working memory performance in the novel object recognition task. Furthermore chronic application
of HDACi intraperitoneal did not enhance working memory performance in untreated
mice in the Y-maze task.
These results indicate a possible global epigenetic deregulation in the schizophrenic pathophysiology
and an epigenetic regulation of working memory-relevant receptors. Nevertheless
HDAC inhibition did not result in altered working memory function | de |
| dc.contributor.coReferee | Oppermann, Martin Prof. Dr. | |
| dc.subject.ger | Schizophrenie | de |
| dc.subject.ger | Epigenetik | de |
| dc.subject.ger | Arbeitsgedächtnis | de |
| dc.subject.ger | Histonacetylierung | de |
| dc.subject.eng | schizophrenia | de |
| dc.subject.eng | epigenetics | de |
| dc.subject.eng | working memory | de |
| dc.subject.eng | histone acetylation | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-0023-963D-C-4 | |
| dc.affiliation.institute | Medizinische Fakultät | de |
| dc.subject.gokfull | Psychiatrie (PPN619876344) | de |
| dc.description.embargoed | 2015-10-20 | |
| dc.identifier.ppn | 836298969 | |