TY  - JOUR
A1  - Schiele, Miriam A.
A1  - Ziegler, Christiane
A1  - Kollert, Leonie
A1  - Katzorke, Andrea
A1  - Schartner, Christoph
A1  - Busch, Yasmin
A1  - Gromer, Daniel
A1  - Reif, Andreas
A1  - Pauli, Paul
A1  - Deckert, Jürgen
A1  - Herrmann, Martin J.
A1  - Domschke, Katharina
T1  - Plasticity of Functional MAOA Gene Methylation in Acrophobia
JF  - International Journal of Neuropsychopharmacology
N2  - Epigenetic mechanisms have been proposed to mediate fear extinction in animal models. Here, MAOA methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells before and after a 2-week exposure therapy in a sample of n = 28 female patients with acrophobia as well as in n = 28 matched healthy female controls. Clinical response was measured using the Acrophobia Questionnaire and the Attitude Towards Heights Questionnaire. The functional relevance of altered MAOA methylation was investigated by luciferase-based reporter gene assays. MAOA methylation was found to be significantly decreased in patients with acrophobia compared with healthy controls. Furthermore, MAOA methylation levels were shown to significantly increase after treatment and correlate with treatment response as reflected by decreasing Acrophobia Questionnaire/Attitude Towards Heights Questionnaire scores. Functional analyses revealed decreased reporter gene activity in presence of methylated compared with unmethylated pCpGfree_MAOA reporter gene vector constructs. The present proof-of-concept psychotherapy-epigenetic study for the first time suggests functional MAOA methylation changes as a potential epigenetic correlate of treatment response in acrophobia and fosters further investigation into the notion of epigenetic mechanisms underlying fear extinction.
KW  - monoamine oxidase A
KW  - anxiety
KW  - extinction
KW  - epigenetics
KW  - DNA methylation
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228571
VL  - 21
IS  - 9
ER  - 
TY  - JOUR
A1  - Sun, Ping
A1  - Ortega, Gabriela
A1  - Tan, Yan
A1  - Hua, Qian
A1  - Riederer, Peter F.
A1  - Deckert, Jürgen
A1  - Schmitt-Böhrer, Angelika G.
T1  - Streptozotocin impairs proliferation and differentiation of adult hippocampal neural stem cells in vitro-correlation with alterations in the expression of proteins associated with the insulin system
JF  - Frontiers in Aging Neuroscience
N2  - Rats intracerebroventricularily (icv) treated with streptozotocin (STZ), shown to generate an insulin resistant brain state, were used as an animal model for the sporadic form of Alzheimer's disease (sAD). Previously, we showed in an in vivo study that 3 months after STZ icv treatment hippocampal adult neurogenesis (AN) is impaired. In the present study, we examined the effects of STZ on isolated adult hippocampal neural stem cells (NSCs) using an in vitro approach. We revealed that 2.5 mM STZ inhibits the proliferation of NSCs as indicated by reduced number and size of neurospheres as well as by less BrdU-immunoreactive NSCs. Double immunofluorescence stainings of NSCs already being triggered to start with their differentiation showed that STZ primarily impairs the generation of new neurons, but not of astrocytes. For revealing mechanisms possibly involved in mediating STZ effects we analyzed expression levels of insulin/glucose system-related molecules such as the glucose transporter (GLUT) 1 and 3, the insulin receptor (IR) and the insulin-like growth factor (IGF) 1 receptor. Applying quantitative Real time-PCR (qRT-PCR) and immunofluorescence stainings we showed that STZ exerts its strongest effects on GLUT3 expression, as GLUT3 mRNA levels were found to be reduced in NSCs, and less GLUT3-immunoreactive NSCs as well as differentiating cells were detected after STZ treatment. These findings suggest that cultured NSCs are a good model for developing new strategies to treat nerve cell loss in AD and other degenerative disorders.
KW  - Alzheimer’s disease
KW  - streptozotocin
KW  - proliferation
KW  - neural stem cells
KW  - insulin-like growth factor 1 receptor
KW  - insulin receptor
KW  - glucose transporter
KW  - differentiation
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176741
VL  - 10
IS  - 145
ER  -