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von Wolff G.,Max Planck Institute of Psychiatry | Avrabos C.,Max Planck Institute of Psychiatry | Stepan J.,Max Planck Institute of Psychiatry | Wurst W.,Max Planck Institute of Psychiatry | And 6 more authors.
Journal of Psychiatric Research | Year: 2011

Corticotropin-releasing hormone (CRH) is thought to play an important role in the pathophysiology of stress-related psychiatric disorders, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). However, knowledge about the actions of CRH at the neuronal network level is only scarce. Here, we examined whether CRH affects neuronal activity propagation through the hippocampal formation (HF), a brain region which is likely to be involved in MDD and PTSD. For this purpose, we applied voltage-sensitive dye imaging (VSDI) to specifically cut hippocampal brain slices obtained from adult mice. This approach allowed us to investigate evoked neuronal activity propagation through the HF with micrometer spatial and millisecond temporal resolution. Application of CRH (50 nM) to slices increased neuronal activity propagation from the dentate gyrus (DG) to the CA1 subfield. This effect of CRH was caused by amplification of neuronal excitation on its passage through the HF and absent in mice lacking the CRH receptor type 1 (CRHR1). In conclusion, our study presents a VSDI assay for the investigation of neuronal activity propagation through the HF and demonstrates that CRH, via CRHR1, enhances this activity propagation. This effect of CRH might contribute to alterations of memory formation seen in MDD and PTSD. Moreover, it could influence hippocampal regulation of hypothalamic-pituitary-adrenal axis (HPA-axis) activity. © 2010 Elsevier Ltd.


Sim N.,Durham University | Gottschalk S.,Helmholtz Center Munich | Pal R.,Durham University | Delbianco M.,Durham University | And 10 more authors.
Chemical Communications | Year: 2015

The cellular localisation and binding specificity of two NMDAR-targeted near-IR imaging probes has been examined by microscopy, followed by exemplification of MSOT to monitor simulated glutamate bursts in cellulo and a preliminary study in mice observing the signal in the brain. © The Royal Society of Chemistry.


Schulz S.,TU Munich | Schulz S.,Research Unit for Environmental Genomics | Giebler J.,Helmholtz Center for Environmental Research | Chatzinotas A.,Helmholtz Center for Environmental Research | And 5 more authors.
ISME Journal | Year: 2012

Alkanes are major constituents of plant-derived waxy materials. In this study, we investigated the abundance, community structure and activity of bacteria harbouring the alkane monooxygenase gene alkB, which catalyses a major step in the pathway of aerobic alkane degradation in the litter layer, the litter-soil interface and in bulk soil at three time points during the degradation of maize and pea plant litter (2, 8 and 30 weeks) to improve our understanding about drivers for microbial performance in different soil compartments. Soil cores of different soil textures (sandy and silty) were taken from an agricultural field and incubated at constant laboratory conditions. The abundance of alkB genes and transcripts (by qPCR) as well as the community structure (by terminal restriction fragment polymorphism fingerprinting) were measured in combination with the concentrations and composition of alkanes. The results obtained indicate a clear response pattern of all investigated biotic and abiotic parameters depending on the applied litter material, the type of soil used, the time point of sampling and the soil compartment studied. As expected the distribution of alkanes of different chain length formed a steep gradient from the litter layer to the bulk soil. Mainly in the two upper soil compartments community structure and abundance patterns of alkB were driven by the applied litter type and its degradation. Surprisingly, the differences between the compartments in one soil were more pronounced than the differences between similar compartments in the two soils studied. This indicates the necessity for analysing processes in different soil compartments to improve our mechanistic understanding of the dynamics of distinct functional groups of microbes. © 2012 International Society for Microbial Ecology All rights reserved.


Waltereit R.,University of Heidelberg | Leimer U.,University of Heidelberg | Von Bohlen Und Halbach O.,University of Greifswald | Panke J.,University of Heidelberg | And 27 more authors.
FASEB Journal | Year: 2012

Mutations in the SRGAP3 gene residing on chromosome 3p25 have previously been associated with intellectual disability. Genome-wide association studies have also revealed SRGAP3, together with genes from the same cellular network, as risk genes for schizophrenia. SRGAP3 regulates cytoskeletal dynamics through the RHO protein RAC1. RHO proteins are known to be involved in cytoskeletal reorganization during brain development to control processes such as synaptic plasticity. To elucidate the importance of SRGAP3 in brain development, we generated Srgap3-knockout mice. Ten percent of these mice developed a hydrocephalus and died before adulthood. Surviving mice showed various neuroanatomical changes, including enlarged lateral ventricles, white matter tracts, and dendritic spines together with molecular changes, including an increased basal activity of RAC1. Srgap3-/- mice additionally exhibited a complex behavioral phenotype. Behavioral studies revealed an impaired spontaneous alternation and social behavior, while long-term memory was unchanged. The animals also had tics. Lower locomotor activity was observed in male Srgap3-/- only. Srgap3-/- mice showed increased methylphenidate stimulation in males and an impaired prepulse inhibition in females. Together, the results show neurodevelopmental aberration in Srgap3 -/- mice, with many of the observed phenotypes matching several schizophreniarelated intermediate phenotypes. Mutations of SRGAP3 may thus contribute to various neurodevelopmental disorders. © FASEB.


Ehm O.,Institute of Developmental Genetics | Goritz C.,Karolinska Institutet | Covic M.,Institute of Developmental Genetics | Schaffner I.,Institute of Developmental Genetics | And 11 more authors.
Journal of Neuroscience | Year: 2010

The generation of new neurons from neural stem cells in the adult hippocampal dentate gyrus contributes to learning and mood regulation. To sustain hippocampal neurogenesis throughout life, maintenance of the neural stem cell pool has to be tightly controlled. We found that the Notch/RBPJκ- signaling pathway is highly active in neural stem cells of the adult mouse hippocampus. Conditional inactivation of RBPJκ in neural stem cells in vivo resulted in increased neuronal differentiation of neural stem cells in the adult hippocampus at an early time point and depletion of the Sox2-positive neural stem cell pool and suppression of hippocampal neurogenesis at a later time point. Moreover, RBPJκ-deficient neural stem cells displayed impaired self-renewal in vitro and loss of expression of the transcription factor Sox2. Interestingly, we found that Notch signaling increases Sox2 promoter activity and Sox2 expression in adult neural stem cells. In addition, activated Notch and RBPJκ were highly enriched on the Sox2 promoter in adult hippocampal neural stem cells, thus identifying Sox2 as a direct target of Notch/RBPJκ signaling. Finally, we found that overexpression of Sox2 can rescue the self-renewal defect in RBPJκ-deficient neural stem cells. These results identify RBPJκ-dependent pathways as essential regulators of adult neural stem cell maintenance and suggest that the actions of RBPJκ are, at least in part, mediated by control of Sox2 expression. Copyright © 2010 the authors.

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