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Behavioural and genetic comparison of B6 and 129Sv mouse lines focusing on the anxiety profile and the expression of Lsamp gene

by Le Dong

Institution: Freie Universität Berlin
Year: 2016
Posted: 02/05/2017
Record ID: 2134359
Full text PDF: http://edocs.fu-berlin.de/diss/receive/FUDISS_thesis_000000101959


Abstract

Background: Since inflammation was closely linked to the onset and development of mental disorders, recent studies focus more and more on the contribution of the resident immune cells of the brain the microglia. Evidence from clinical and animal studies has demonstrated a change in the microglial phenotype in both schizophrenia and depressive disorder. Deep brain stimulation (DBS) is a novel treatment for neurological disorders. It has been proved that DBS can effectively ameliorate the symptoms of psychiatric disorders, but the effects of DBS on microglia in schizophrenia and depression are not clear yet. Methods: We were using immunohistochemistry and PCR techniques to investigate the changes of microglia with and without DBS treatment in a rat model of schizophrenia and depressive disorder. Results: In the rat model of schizophrenia, microglial density and soma size in the hippocampus and nucleus accumbens (Nacc) were significantly increased. Deep brain stimulation (DBS) treatment in the medial prefrontal cortex (mPFC) and Nacc effectively attenuated these changes of microglia in both regions. More than that, Nacc-DBS treatment also raised the density of microglia in the mPFC and caudate putamen (CPu) in the schizophrenic rats. In the depressive rat model, the density of microglia in the mPFC was deregulated compared to the control group. However, there was no significant DBS effect detected in the depression model. Furthermore, we confirmed that implantation of electrode can cause an activation of microglia in the targeted region and DBS current reduced microglia activity. Conclusion: The results thus show that there is microglial dysregulation in a rat model of schizophrenia and depression. DBS treatment can normalize microglia density and soma size in both targeted area as well as projection area in schizophrenic rats, but no valuable effect of DBS on microglia can be detected in the rat model of depression. Hintergrund: Neue Erkenntnisse zeigen das Entzündungsreaktionen im Gehirn einen großen Einfluss auf die Entstehung und die Entwicklung von psychischen Erkrankungen haben. Im speziellen zeigen eine steigende Anzahl von Studien den Einfluss von Mikroglia, als Gehirn spezifische Immunzellen, auf diese Erkrankungen. Sowohl klinische als auch Tier basierte Studien zeigen eine phänotypische Veränderung von Mikroglia in der Schizophrenie als auch depressiven Erkrankungen. Weitere Studien zeigen, dass eine Tiefenhirnstimulation (eng. Deep Brain Stimulation = DBS) die Symptome von psychischen Erkrankungen lindern kann. Jedoch ist der Effekt einer Tiefenhirnstimulation auf Mikroglia noch nicht aufgeklärt. Methoden: Um die phänotypischen Veränderungen in Mikroglia aufzuklären wurden immunhistochemische Färbungen und qualitative RT-PCR von wahlweise eines Rattenmodels für Schizophrenie oder depressive Erkrankungen mit und ohne Tiefenhirnstimulationsbehandlung durchgeführt. Ergebnisse: Im Schizophrenierattenmodel ist sowohl die Dichte als auch die Größe des Zytosomas der Mikrolgia im Hippocampus und…

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