Artikel
Effects of deep brain stimulation on glial cells in animal models of depression and schizophrenia
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Autoren
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Regina Rita Schweibold
- AG Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin Berlin-Buch; Klinik für Neurochirurgie, Helios Klinikum Berlin-Buch
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Susanne A. Wolf
- AG Zelluläre Neurowissenschaften, Max-Delbrück-Centrum für Molekulare Medizin Berlin-Buch
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Christine Winter
- Klinik und Poliklinik für Psychiatrie und Psychotherapie / Experimentelle Psychiatrie, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
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Jürgen Kiwit
- Klinik für Neurochirurgie, Helios Klinikum Berlin-Buch
| Veröffentlicht: | 2. Juni 2015 |
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| Veröffentlicht mit Erratum: | 15. Juni 2015 |
Gliederung
Text
Objective: The discovery of new glial functions coincides with growing evidence of the involvement of glia in the neuropathology of mood disorders.
a) Both preclinical and clinical studies suggest that inflammation leading to microglial activation, astroglial loss, and inappropriate glutamate receptor activation disrupt the balance of neuroprotective vs. neurotoxic effects in the brain, potentially leading to depression.
b) Schizophrenia is a not fully understood severe mental disorder. Recent studies show that immunological factors might be the cause for the structural and functional changes in the CNS. Thererfore, the Poly I:C - model is an established animal-model to investigate mechanisms of schizophrenia.
c) Deep Brain Stimulation (DBS) is a common therapy for movement disorders. Animal studies and (small) clinical studies provided evidence for an effect of DBS in depression, obsessive compulsive disorder and addiction. Schizophrenia is discussed as an aim for DBS. Animal studies are needed to detect brain regions for stimulation.
Method: a) 20 rats of the "Flinders Sensitive Line" and "Flinders Resistant Line" (both ZI Mannheim) underwent DBS in the Nucleus accumbens (Nacc) and the Subgenual Cingulum (Cg25). We evaluated via confocal microscopy microglial density in the hippocampus.
b) 40 Harlan-Wistar-rats will be included in an investigation on density and activation of microglia in the Poly I:C model until June 2015. Until now, 8 animals underwent DBS (5 rats Poly I:C, 3 rats NaCl 0,9%) of the medial prefrontal cortex (mPFC). 5 rats (3 rats Poly I:C, 2 rats NaCl 0,9%) received a sham electrode. Behavioural testing will be performed. Investigations on microglial changes in different brain regions will be assessed via FACS and PCA.
Results: a) In the acute DBS group, we saw a significant higher densitiy in the depressive Nacc-DBS-group compared to the control Nacc-DBS-group and in the depressive Nacc-DBS-group compared to the control Nacc-Sham-group. The chronic stimulated groups are about to be analyzed.
b) Since we started the Poly I:C-study in 10/14, data analysis will be provided in June 2015.
Conclusions: Microglial changes after DBS in mental disorders have so far never been investigated. Our studies might not only provide further information about the origin and neurobiological mechanisms of depression and schizophrenia, but on microglial function in general. Moreover we will receive further details about the effects of DBS in different brain regions.
