A5000210736- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Receptor Mechanisms and Signaling
- Stress Responses and Cortisol
- Neuropeptides and Animal Physiology
- Tryptophan and brain disorders
- Neuroendocrine regulation and behavior
- Treatment of Major Depression
- Parkinson's Disease Mechanisms and Treatments
- Neural dynamics and brain function
- Nuclear Receptors and Signaling
- Advanced Scientific Research Methods
- Invertebrate Immune Response Mechanisms
- Neurobiology and Insect Physiology Research
- Memory and Neural Mechanisms
- Science, Research, and Medicine
- Insect Resistance and Genetics
- Nerve injury and regeneration
- MicroRNA in disease regulation
- Zebrafish Biomedical Research Applications
- Alzheimer's disease research and treatments
- Decision-Making and Behavioral Economics
- Mental Health Research Topics
- Chemical Reactions and Isotopes
- Pharmacogenetics and Drug Metabolism
Maj Institute of Pharmacology
2012-2024
Polish Academy of Sciences
2014-2024
German Cancer Research Center
2008-2020
Heidelberg University
2008-2020
Institute of Pharmacology
2010-2018
DKFZ-ZMBH Alliance
2014
Institute of Organic Chemistry
2002
Wrocław University of Science and Technology
1996-2002
Dicer-dependent noncoding RNAs, including microRNAs (miRNAs), play an important role in a modulation of translation mRNA transcripts necessary for differentiation many cell types. In vivo experiments using type-specific Dicer1 gene inactivation neurons showed its essential neuronal development and survival. However, little is known about the consequences loss miRNAs adult, fully differentiated neurons. To address this question, we used inducible variant Cre recombinase (tamoxifen-inducible...
We investigated the efficacy of local intraplantar (i.pl.) injection peptide and non-peptide mu-, delta- kappa-opioid receptor agonists in rat models inflammatory neuropathic pain. Locally applied dose-dependently reduced formalin-induced flinching inflamed paw induced antiallodynic antihyperalgesic effects sciatic nerve ligation-induced These were mediated by peripheral opioid receptors localized at side tissue/nerve injury, as was demonstrated selective non-selective antagonists. The...
Sepsis is controlled by endogenous glucocorticoids (GCs). Previous studies provided evidence that crosstalk of the monomeric GC receptor (GR) with proinflammatory transcription factors crucial mechanism underlying suppressive effect. Here we demonstrate mice a dimerization-deficient GR (GRdim) are highly susceptible to sepsis in 2 different models, namely cecal ligation and puncture lipopolysaccharide (LPS)-induced septic shock. TNF-α normally regulated these mice, but down-regulation IL-6...
Induction of specific gene expression patterns in response to activity confers functional plasticity neurons. A principal role the regulation these processes has been ascribed cAMP responsive element binding protein (CREB). Using genome-wide profiling mice lacking CREB forebrain, accompanied by deletion modulator (CREM), we here show that proteins activity-induced is surprisingly selective and highly context dependent. Thus, only a very restricted subset genes (i.e., Gadd45b or Nr4a2)...
Systemic inflammation causes malaise and general feelings of discomfort. This fundamental aspect the sickness response reduces quality life for people suffering from chronic inflammatory diseases is a nuisance during mild infections like common colds or flu. To investigate how perceived as unpleasant negative affect, we used behavioral test in which mice avoid an environment that they have learned to associate with inflammation-induced Using combination cell-type–specific gene deletions,...
Understanding the psychobiological basis of relapse remains a challenge in developing therapies for drug addiction. Relapse cocaine addiction often occurs following exposure to environmental stimuli previously associated with taking. The metabotropic glutamate receptor, mGluR5, is potentially important this respect; it plays central role several forms striatal synaptic plasticity proposed underpin associative learning and memory processes that enable drug-paired acquire incentive...
The NMDA receptor antagonist ketamine was found to act as a fast-acting antidepressant. effects of single treatment were reported persist for days weeks, even in otherwise treatment-refractory cases. Identification the mechanisms underlying ketamine's antidepressant action may permit development novel drugs, with similar clinical properties but lacking psychotomimetic, sedative and other side effects. We applied whole-genome microarray profiling analyze detailed time-course (1, 2, 4 8 h)...
A solid-state approach was used to synthesize compound PZ-1190, a multitarget ligand for serotonin and dopamine receptors with potential antipsychotic activity in rodents. Compared the classical batch synthesis approach, developed multistep mechanochemical protocol improved overall yield (from 32% 56%), reduced reaction time 42 4 h), decreased use of toxic reagents organic solvents. All synthesized intermediates PZ-1190 were isolated high purity by extraction without requirement...
L-3,4-Dihydroxyphenylalanine (L-DOPA) is effective at alleviating motor impairments in Parkinson's disease (PD) patients but has mixed effects on nonmotor symptoms and causes adverse after prolonged treatment. Here, we analyzed the spatial profile of L-DOPA-induced gene expression forebrain mice with an inducible progressive loss dopaminergic neurons (the TIF-IADATCreERT2 strain), a focus similarities differences areas relevant to different PD symptoms. The animals received 14-day L-DOPA...
The serum response factor (SRF) is a key regulator of neural development and cellular plasticity, which enables it to act as long-term adaptations in neurons. Here we performed comprehensive analysis SRF function the murine dopamine system. We found that loss dopaminoceptive, but not dopaminergic, neurons responsible for hyperactivity syndrome, characterized by reduced body weight into adulthood, enhanced motor activity, deficits habituation processes. Most important, also develops when...
Corticosteroid treatment is an established therapy for preterm infants, and germline inactivation of the glucocorticoid receptor (GR) gene in mouse leads to respiratory failure postnatal lethality. Although glucocorticoids have been thought critically act epithelial cells inducing functional maturation lung, GR exclusively epithelium developing murine lung did not impair survival. In contrast, mice lacking specifically mesenchyme-derived displayed a phenotype strongly reminiscent knockout...
Repeated administration of morphine is associated with the development tolerance, yet mechanism underlying this phenomenon still poorly understood. Recent evidence implicating glycogen synthase kinase 3 (GSK3) in opioid receptor signaling pathways has prompted us to investigate its role tolerance. Administration 10 mg/kg i.p. Wistar rats twice daily for 8 days resulted complete tolerance analgesic effects as measured by tail-flick test. When injections were preceded intrathecal (i.t.) either...
The persistent nature of addiction has been associated with activity-induced plasticity neurons within the striatum and nucleus accumbens (NAc). To identify molecular processes leading to these adaptations, we performed Cre/loxP-mediated genetic ablations two key regulators gene expression in response activity, Ca(2+)/calmodulin-dependent protein kinase IV (CaMKIV) its postulated main target, cAMP-responsive element binding (CREB). We found that acute cocaine-induced was largely unaffected...
Decreased rRNA synthesis and nucleolar disruption, known as stress, are primary signs of cellular stress associated with aging neurodegenerative disorders. Silencing rDNA occurs during early stages Alzheimer's disease (AD) may play a role in dementia. Moreover, aberrant regulation the protein machinery is present brain suicide victims implicates epigenetic modulation rRNA. Recently, we developed unique mouse models characterized by neurons. We inhibited RNA polymerase I genetic ablation...
Here, we describe a new model of voluntary alcohol drinking by group-housed mice. The employs sensor-equipped cages that track the behaviors individual animals via implanted radio chips. After were allowed intermittent access to (three 24 h intervals every week) for 4 weeks, proportions licks directed toward bottles containing 50.9% and 39.6% male female mice, respectively. We used three approaches (i.e., quinine adulteration, progressive ratio schedule involving risk punishment) test...
It is suggested that striatal cAMP responsive element binding protein (CREB) regulates sensitivity to psychostimulants. To test the cell-specificity of this hypothesis we examined effects a dominant-negative CREB variant expressed in dopamine receptor D1 (D1R) neurons on cocaine-induced behaviors. A transgenic mouse strain was generated by pronuclear injection BAC-derived transgene harboring A-CREB sequence under control D1R gene promoter. Compared wild-type, drug-naïve mutants showed...
Abstract Plasticity of the brain’s dopamine system plays a crucial role in adaptive behavior by regulating appetitive motivation and control reinforcement learning. In this study, we investigated drug- natural-reward conditioned behaviors mouse model which NMDA receptor-dependent plasticity dopaminoceptive neurons was disrupted. We generated transgenic line with inducible selective inactivation NR1 subunit expressing D1 receptors (the D1CreERT2 mice). Whole-cell recordings spontaneous EPSCs...
Abstract The role of changes in dopamine neuronal activity during the development symptoms affective disorders remains controversial. Here, we show that inactivation NMDA receptors on dopaminergic neurons adult mice led to disorder-like symptoms. loss altered and caused complete NMDA-insensitivity dopamine-like neurons. Mutant exhibited increased immobility forced swim test a decrease social interactions. Mutation also reduced saccharin intake, however preference sweet taste was not...
According to psychological theories, cognitive distortions play a pivotal role in the aetiology and recurrence of mood disorders. Although clinical evidence for coexistence depression altered sensitivity performance feedback is relatively coherent, we still do not know whether increased or decreased positive negative associated with 'pro-depressive' profile healthy subjects. Our research has been designed answer this question, here, present first steps that direction. Using rat version...