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Burg bei Magdeburg, Germany

Bose T.,Leibniz Institute of Neurobiology | Cieslar-Pobuda A.,Linkoping University | Cieslar-Pobuda A.,Silesian University of Technology | Wiechec E.,Linkoping University
Cell Death and Disease | Year: 2015

Ion channels are abundantly expressed in both excitable and non-excitable cells, thereby regulating the Ca2+ influx and downstream signaling pathways of physiological processes. The immune system is specialized in the process of cancer cell recognition and elimination, and is regulated by different ion channels. In comparison with the immune cells, ion channels behave differently in cancer cells by making the tumor cells more hyperpolarized and influence cancer cell proliferation and metastasis. Therefore, ion channels comprise an important therapeutic target in anti-cancer treatment. In this review, we discuss the implication of ion channels in regulation of Ca2+ homeostasis during the crosstalk between immune and cancer cell as well as their role in cancer progression. © 2015 Macmillan Publishers Limited. All rights reserved.

Huchtemann T.,University Hospital Magdeburg | Kortvelyessy P.,University Hospital Magdeburg | Feistner H.,University Hospital Magdeburg | Heinze H.J.,University Hospital Magdeburg | And 2 more authors.
Epilepsy and Behavior | Year: 2015

Introduction: Recently, a mouse model showed that progranulin, a mediator in neuroinflammation and a neuronal growth factor, was elevated in the hippocampus after status epilepticus (SE). This elevated level might mirror compensating neuronal mechanisms after SE. Studies concerning neuronal recovery and neuroprotective mechanisms after SE in humans are scarce, so we tested for progranulinin the cerebrospinal fluid (CSF) after various types of SE. Method: We performed a retrospective analysis of progranulin levels in CSF in patients (n. =. 24) who underwent lumbar puncture as part of diagnostic workup after having SE and in patients after having one single tonic-clonic seizure who comprised the control group (n. =. 8). Results: In our group with SE, progranulin levels in CSF were not significantly elevated compared to our control group. Furthermore, there was no correlation between progranulin levels and the time interval between lumbar puncture and SE. Additionally, in cases of higher CSF progranulin levels, we found no impact on the clinical outcome after SE. Conclusion: Although our cohort is heterogeneous and not fully sufficient, we conclude that progranulin in CSF is not elevated after SE in our cohort. Therefore, our results do not suggest a change in cerebral progranulin metabolism as a possible neuroregenerative or neuroprotective mechanism in humans after SE in acute and subacute phases. A larger cohort study is needed to further strengthen this result.This article is part of a Special Issue entitled "Status Epilepticus". © 2015 Elsevier Inc.

Janitzky K.,Otto Von Guericke University of Magdeburg | Janitzky K.,Leibniz Institute of Neurobiology | Peine A.,Otto Von Guericke University of Magdeburg | Krober A.,Otto Von Guericke University of Magdeburg | And 3 more authors.
Behavioural Brain Research | Year: 2014

The bed nucleus of the stria terminalis (BNST) is an important region for 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) predator odor-induced stress responses in mice. It is sexually dimorphic and a region for corticotropin-releasing factor (CRF)-enhanced stress responses. Dense GABAergic and CRF input from the amygdala to the BNST gives point to relevant interactions between CRF and GABA activity in these brain regions. Hence, to investigate sexual dimorphism of stress-induced neuronal changes, we studied effects of acute TMT exposure on CRF mRNA expression in stress-related brain regions in male and female GAD67 mice and their wild-type littermates. In GAD67 mice, heterozygous knock-in of GFP in GABAergic neurons caused a 50% decrease of GAD67 protein level in the brain [91,99]. Results show higher CRF mRNA levels in the BNST of male but not female GAD67 mice after TMT and control odor exposure. While CRF neurons in the BNST are predominantly GABAergic and CRF enhances GABAergic transmission in the BNST [20,51], the deficit in GABAergic transmission in GAD67 mice could induce a compensatory CRF increase. Sexual dimorphism of the BNST with greater density of GABA-ir neurons in females could explain the differences in CRF mRNA levels between male and female GAD67 mice.Effects of odor exposure were studied in a radial arm maze (RAM) task. Results show impaired retrieval of spatial memory after acute TMT exposure in both sexes and genotypes. However, only GAD67 mice show increased working memory errors after control odor exposure.Our work elicits GAD67 mice as a model to further study interactions of GABA and CRF in the BNST for a better understanding of how sex-specific characteristics of the brain may contribute to differences in anxiety- and stress-related psychological disorders. © 2014 Elsevier B.V.

Malatynska E.,Lilly Research Labs Lilly Corporate Center | Steinbusch H.W.M.,Maastricht University | Redkozubova O.,Russian Academy of Sciences | Bolkunov A.,Russian Academy of Sciences | And 5 more authors.
Experimental Gerontology | Year: 2012

The prevalence of depression increases with aging. We hypothesized that like humans, old animals exhibit anhedonic-like behavior, along with signs of behavioral despair. In rodents, anhedonia, a reduced sensitivity to reward, which is listed as a core feature of major depression in the DSM-IVR, can be measured by a decrease in intake of and preference for sweet solutions. Here, sucrose intake, forced swimming, immobility in the modified tail suspension test, novelty exploration, grooming, anxiety and locomotor activity were compared in naïve 3- and 18-month-old male C57BL/6 mice. The absolute amounts and the ratio of consumed 1% sucrose solution to water intake was significantly smaller in 18-month-old mice than in 3-month-old mice. The consumption of 5%-sucrose solution requiring high levels of drinking effort, novelty exploration in two setups and grooming behavior in the splash test were reduced in older animals. Analysis of other behaviors suggested that the above-mentioned signs of anhedonic-like traits were unlikely to be attributable to the potential effect of aging on metabolic needs for water, taste perception, motor capabilities or the induction of essential anxiety and neophobia. A 4-week treatment with the antidepressant imipramine (7. mg/kg/day) or dimebon, a compound with suggested neuroprotective proneurogenic properties (1. mg/kg/day) restored sucrose intake and preference in 18-month-old mice. Meanwhile, young and old mice showed no differences in the parameters of behavioral despair evaluated in the forced swim and modified tail suspension tests. Thus, the behavioral profile of aged mice parallels that of humans with elderly depression, in whom the symptoms of hedonic deficits typically outweigh affective disturbances. The assessment of anhedonic-like traits with the sucrose preference test in 18-month-old mice will be useful in preclinical studies of elderly depression. © 2012 Elsevier Inc.

Meyer A.F.,University of Oldenburg | Diepenbrock J.-P.,Leibniz Institute of Neurobiology | Ohl F.W.,Leibniz Institute of Neurobiology | Ohl F.W.,Otto Von Guericke University of Magdeburg | Anemuller J.,University of Oldenburg
International IEEE/EMBS Conference on Neural Engineering, NER | Year: 2013

Neurons integrating sensory stimulus features are found in many brain areas up to cortical level, and their understanding is essential for building and improving neural prostheses. Here, we focus on auditory neural coding in the inferior colliculus (IC). Much work has been conducted to identify the primary spectro-temporal sound features. However, a description of how reliable these features are encoded at IC level remains an open question. In a simplified model, the encoding process can be described by a linear integrator followed by a threshold nonlinearity that creates a binary spike sequence. To account for variability in neural responses, coding noise has to be taken into account. However, coding noise reduces the certainty about the stimulus features encoded. Traditional approaches to quantify the amount of noise based on information theory are prone to sampling bias and cannot be bounded in a simply way, making it hard to interpret the results obtained and to compare them across neural populations. Here, we reformulate neural coding as a spike detection task and show that methods from signal detection theory allow an alternative description to quantify coding noise. Using neural responses from the IC in Mongolian gerbils to acoustic stimuli, we demonstrate that this approach allows a reliable description of neural coding noise, particularly in the small data limit, while being highly correlated with information-theoretic quantities in the large-data regime. © 2013 IEEE.

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