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Burg bei Magdeburg, Germany

Ludwig M.,University of Edinburgh | Tobin V.A.,University of Edinburgh | Callahan M.F.,Tensive Controls, Inc. | Papadaki E.,University of Edinburgh | And 4 more authors.
Journal of Neuroendocrinology | Year: 2013

Intranasal administration has been widely used to investigate the effects of the neuropeptides vasopressin and oxytocin on human behaviour and neurological disorders, although exactly what happens when these neuropeptides are administered intranasally is far from clear. In particular, it is not clear whether a physiological significant amount of peptide enters the brain to account for the observed effects. In the present study, we investigated whether the intranasal administration of vasopressin and oxytocin to rats induces the expression of the immediate-early gene product Fos in brain areas that are sensitive to centrally-administered peptide, whether it alters neuronal activity in the way that centrally-administered peptide does, and whether it affects behaviour in the ways that are expected from studies of centrally-administered peptide. We found that, whereas i.c.v. injection of very low doses of vasopressin or oxytocin increased Fos expression in several distinct brain regions, intranasal administration of large doses of the peptides had no significant effect. By contrast to the effects of vasopressin applied topically to the main olfactory bulb, we saw no changes in the electrical activity of olfactory bulb mitral cells after intranasal vasopressin administration. In addition, vasopressin given intranasally had no significant effects on social recognition or short-term recognition memory. Finally, intranasal infusions of vasopressin had no significant effects on the parameters monitored on the elevated plus maze, a rodent model of anxiety. Our data obtained in rats suggest that, after intranasal administration, significant amounts of vasopressin and oxytocin do not reach areas in the brain at levels sufficient to change immediate early gene expression, neural activity or behaviour in the ways described for central administration of the peptides. © 2013 British Society for Neuroendocrinology. Source


Zelena D.,Hungarian Academy of Sciences | Pinter O.,Hungarian Academy of Sciences | Langnaese K.,Otto Von Guericke University of Magdeburg | Richter K.,Otto Von Guericke University of Magdeburg | And 4 more authors.
Journal of Neuroendocrinology | Year: 2013

Adult male Brattleboro rats were used to investigate the impact of the congenital absence of vasopressin on the release pattern of oxytocin (OXT) within the hypothalamic supraoptic nucleus (SON) in response to a 10-min forced swimming session and osmotic stimulation. Both immunohistochemical and in situ hybridisation data suggest that vasopressin-deficient animals have more oxytocin-synthesising neurones in the SON than homozygous wild-type controls. Unexpectedly, both forced swimming and peripheral osmotic stimulation resulted in a blunted release profile of oxytocin within the SON of vasopressin-deficient rats compared to controls. A similar intranuclear OXT response to direct osmotic stimulation of the SON by retrodialysis with hypertonic Ringer's solution in both genotypes confirmed the capability of SON neurones to locally release oxytocin in vasopressin-deficient rats, indicating an altered processing of information originating from multisynaptic inputs rather than a deficit in release capacity. Taken together with data obtained in previous studies, the present findings provide evidence suggesting that autocrine and paracrine signalling of magnocellular neurones differs within the paraventricular nucleus and the SON. Thus, significant alterations in intra-SON oxytocin mRNA levels cannot easily be extrapolated to intranuclear release profiles and the local signal intensity of this neuropeptide after physiological stimulation. © 2013 British Society for Neuroendocrinology. Source


Xie L.,Otto Von Guericke University of Magdeburg | Xie L.,Center for Behavioral Brain science Magdeburg | Korkmaz K.S.,Ege University | Braun K.,Otto Von Guericke University of Magdeburg | And 3 more authors.
Journal of Neurochemistry | Year: 2013

Early life stress (ELS) programs the developing organism and influences the development of brain and behavior. We tested the hypothesis that ELS-induced histone acetylations might alter the expression of synaptic plasticity genes that are critically involved in the establishment of limbic brain circuits. Maternal separation (MS) from postnatal day 14-16 was applied as ELS and two immediate early genes underlying experience-induced synaptic plasticity, Arc and early growth response 1 (Egr1) were analyzed. We show here that repeated ELS induces a rapid increase of Arc and Egr1 in the mouse hippocampus. Furthermore, immunoblotting revealed that these changes are paralleled by histone modifications, reflected by increased acetylation levels of H3 and H4. Most importantly, using native Chromatin immunoprecipitation quantitative PCR (nChIP-qPCR), we show for the first time a correlation between elevated histone acetylation and increased Arc and Egr1 expression in response to ELS. These rapid epigenetic changes are paralleled by increases of dendritic complexity and spine number of hippocampal CA3 pyramidal neurons in ELS animals at weaning age. Our results are in line with our working hypothesis that ELS induces activation of synaptic plasticity genes, mediated by epigenetic mechanisms. These events are assumed to represent early steps in the adaption of neuronal networks to a stressful environment. This study provides evidence that early life stress (ELS) induces rapid epigenetic alterations affecting synaptic plasticity genes in the hippocampus. In particular, ELS resulted in enhanced acetylation of histone H4at the promoter regions of Arc and Egr1 leading to increased expression of these genes. We speculate that the epigenetic changes are related to stress-induced alterations in dendritic morphology observed in parallel. © 2013 International Society for Neurochemistry. Source


Richter A.,Leibniz Institute for Neurobiology | Richter S.,Leibniz Institute for Neurobiology | Richter S.,University of Salzburg | Barman A.,Leibniz Institute for Neurobiology | And 15 more authors.
Frontiers in Human Neuroscience | Year: 2013

Dopamine has been implicated in the fine-tuning of complex cognitive and motor function and also in the anticipation of future rewards. This dual function of dopamine suggests that dopamine might be involved in the generation of active motivated behavior. The DRD2 TaqIA polymorphism of the dopamine D2 receptor gene (rs1800497) has previously been suggested to affect striatal function with carriers of the less common A1 allele exhibiting reduced striatal D2 receptor density and increased risk for addiction. Here we aimed to investigate the influences of DRD2 TaqIA genotype on the modulation of interference processing by reward and punishment. 46 young, healthy volunteers participated in a behavioral experiment, and 32 underwent functional magnetic resonance imaging (fMRI). Participants performed a flanker task with a motivation manipulation (monetary reward, monetary loss, neither, or both). Reaction times (RTs) were shorter in motivated flanker trials, irrespective of congruency. In the fMRI experiment motivation was associated with reduced prefrontal activation during incongruent versus congruent flanker trials, possibly reflecting increased processing efficiency. DRD2 TaqIA genotype did not affect overall RTs, but interacted with motivation on the congruency-related RT differences, with A1 carriers showing smaller interference effects to reward alone and A2 homozygotes exhibiting a specific interference reduction during combined reward and punishment trials. In fMRI, anterior cingulate activity showed a similar pattern of genotype-related modulation. Additionally, A1 carriers showed increased anterior insula activation relative to A2 homozygotes. Our results point to a role for genetic variations of the dopaminergic system in individual differences of cognition-motivation interaction. © 2013 Richter, Richter, Barman, Soch, Klein, Assmann, Libeau, Behnisch, Wustenberg, Seidenbecher and Schott. Source


Valenzuela J.C.,Leibniz Institute for Neurobiology Magdeburg | Heise C.,Leibniz Institute for Neurobiology Magdeburg | Heise C.,CNR Institute of Neuroscience | Franken G.,Leibniz Institute for Neurobiology Magdeburg | And 6 more authors.
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2014

Neuronal networks are balanced by mechanisms of homeostatic plasticity, which adjusts synaptic strength via molecular and morphological changes in the pre- and post-synapse. Here, we wondered whether the hyaluronic acid-based extracellular matrix (ECM) of the brain is involved in mechanisms of homeostatic plasticity. We hypothesized that the ECM, being rich in chondroitin sulfate proteoglycans such as brevican, which are suggested to stabilize synapses by their inhibitory effect on structural plasticity, must be remodelled to allow for structural and molecular changes during conditions of homeostatic plasticity. We found a high abundance of cleaved brevican fragments throughout the hippocampus and cortex and in neuronal cultures, with the strongest labelling in perineuronal nets on parvalbuminpositive interneurons. Using an antibody specific for a brevican fragment cleaved by the matrix metalloprotease ADAMTS4, we identified the enzyme as the main brevican-processing protease. Interestingly, we found ADAMTS4 largely associated with synapses. After inducing homeostatic plasticity in neuronal cell cultures by prolonged network inactivation, we found increased brevican processing at inhibitory as well as excitatory synapses, which is in line with the ADAMTS4 subcellular localization. Thus, the ECM is remodelled in conditions of homeostatic plasticity, whichmay liberate synapses to allow for a higher degree of structural plasticity. & 2014 The Authors. Source

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