- Neuroscience and Neuropharmacology Research
- Adipose Tissue and Metabolism
- Stress Responses and Cortisol
- Protease and Inhibitor Mechanisms
- Receptor Mechanisms and Signaling
- Mitochondrial Function and Pathology
- Tryptophan and brain disorders
- Neurogenesis and neuroplasticity mechanisms
- Cellular Mechanics and Interactions
- Cell Image Analysis Techniques
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroendocrine regulation and behavior
- RNA modifications and cancer
- RNA Research and Splicing
- Neuropeptides and Animal Physiology
- Signaling Pathways in Disease
- Axon Guidance and Neuronal Signaling
- Alzheimer's disease research and treatments
- RNA and protein synthesis mechanisms
- Muscle Physiology and Disorders
- Treatment of Major Depression
- Neurotransmitter Receptor Influence on Behavior
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Peptidase Inhibition and Analysis
- Heat shock proteins research
Instytut Biologii Doświadczalnej im. Marcelego Nenckiego
2013-2024
Polish Academy of Sciences
2012-2024
Medizinische Hochschule Hannover
2017-2022
Oslo University Hospital
2022
Institute of Biochemistry and Biophysics, Polish Academy of Sciences
2019-2022
University of Warsaw
2022
Mossakowski Medical Research Institute, Polish Academy of Sciences
2022
Maj Institute of Pharmacology
2022
University of Oslo
2022
AbstractAccurate tRNA processing is crucial for human mitochondrial genome expression, but the mechanisms of mt-tRNA cleavage and key enzymes involved in this process are poorly characterized. At least two activities required proper maturation: RNase P cleaving precursor molecules at 5' end tRNase Z 3' end. In mitochondria only has been identified so far. Using RT-PCR northern blot analyses we found that silencing ELAC2 gene results impaired mt-tRNAs. We demonstrate several tRNAs, encoded on...
The serotonergic system and in particular serotonin 1A receptor (5-HT1AR) are implicated major depressive disorder (MDD). Here we demonstrated that 5-HT1AR is palmitoylated human rodent brains, identified ZDHHC21 as a palmitoyl acyltransferase, whose depletion reduced palmitoylation consequently signaling functions of 5-HT1AR. Two models for depression-like behavior show brain expression attenuated palmitoylation. Moreover, selective knock-down the murine forebrain induced behavior. We also...
Rewiring of synaptic circuitry pertinent to memory formation has been associated with morphological changes in dendritic spines and extracellular matrix (ECM) remodeling. Here, we mechanistically link these processes by uncovering a signaling pathway involving the serotonin 5-HT7 receptor (5-HT7R), metalloproteinase 9 (MMP-9), hyaluronan CD44, small GTPase Cdc42. We highlight physical interaction between 5-HT7R CD44 (identified as an MMP-9 substrate neurons) find that stimulation increases...
Synapses are particularly prone to dynamic alterations and thus play a major role in neuronal plasticity. Dynamic excitatory synapses located at the membranous protrusions called dendritic spines. The ability change synaptic connections involves both morphological level changes postsynaptic receptor composition. We report that endogenous matrix metalloproteinase (MMP) activity promotes structural functional plasticity of local by its effect on glutamate mobility content. used live imaging...
Precise control of dendritic spine density and synapse formation is critical for normal pathological brain functions. Therefore, signaling pathways influencing dendrite outgrowth remodeling remain a subject extensive investigations. Here, we report that prolonged activation the serotonin 5-HT7 receptor (5-HT7R) with selective agonist LP-211 promotes spines facilitates synaptogenesis in postnatal cortical striatal neurons. Critical role 5-HT7R neuronal morphogenesis was confirmed by analysis...
Major depressive disorder is a complex disease resulting from aberrant synaptic plasticity that may be caused by abnormal serotonergic signaling. Using combination of behavioral, biochemical, and imaging methods, we analyze 5-HT7R/MMP-9 signaling dendritic spine in the hippocampus mice treated with selective 5-HT7R agonist (LP-211) model chronic unpredictable stress (CUS)-induced depressive-like behavior. We show acute activation induces behavior an MMP-9-dependent manner post mortem brain...
Abstract Background Quantitative analysis of changes in dendritic spine morphology has become an interesting issue contemporary neuroscience. However, the diversity population might seriously influence result measurements which their is studied. The detection differences between control and test group often compromised by number spines taken for analysis. In order to estimate impact we performed Monte Carlo simulations examining various experimental setups statistical approaches. confocal...
Dendritic spines are small membranous protrusions that extend from neuronal dendrites and harbor the majority of excitatory synapses. Increasing evidence has shown matrix metalloproteinases (MMPs), a family extracellularly acting Zn2+-dependent endopeptidases, able to rapidly modulate dendritic spine morphology. Spine head (SHPs) filopodia-like processes head, representing form postsynaptic structural remodeling in response altered activity. Herein, we show chemically induced long-term...
The precise regulation of synaptic integrity is critical for neuronal network connectivity and proper brain function. Essential aspects the activity localization proteins are regulated by posttranslational modifications. S-palmitoylation a reversible covalent modification cysteine with palmitate. It modulates affinity protein cell membranes membranous compartments. Intracellular palmitoylation dynamics crosstalk other modifications, such as S-nitrosylation. S-nitrosylation thiol nitric oxide...
Modifications of properties the adult sensory cortex by elimination input (deprivation) serves as a model for studying plasticity in brain. We studied effects short- and long-term deprivation (sparing one row vibrissae) upon barrel cortex. The response to stimulation (exploration new environment) spared was examined with [14C]-2-deoxyglucose autoradiography c-Fos immunohistochemistry. Both methods found large increases functional cortical representation vibrissae, extending into parts...
Abstract Activity-dependent remodeling of excitatory connections underpins memory formation in the brain. Serotonin receptors are known to contribute such remodeling, yet underlying molecular machinery remains poorly understood. Here, we employ high-resolution time-lapse FRET imaging neuroblastoma cells and neuronal dendrites establish that activation serotonin receptor 5-HT 4 (5-HT R) rapidly triggers spatially-restricted RhoA activity G13-mediated phosphorylation cofilin, thus locally...
The therapeutic effects of fluoxetine are believed to be due increasing neuronal plasticity and reversing some learning deficits. Nevertheless, a growing amount evidence shows adverse this drug on cognition forms plasticity.To study the chronic treatment, we combine an automated assessment motivation in mice with investigation central amygdala basolateral amygdala. We use immunohistochemistry visualize types perineuronal nets, along DI staining assess dendritic spine morphology. Gel...
Dendritic outgrowth and arborization are important for establishing neural circuit formation. To date, little information exists about the involvement of extracellular matrix (ECM) its cellular receptors in these processes. In our studies, we focus on role dystroglycan (DG), a cell adhesion molecule that links ECM components to actin cytoskeleton, dendritic development branching. Using lentiviral vector deliver short-hairpin RNA (shRNA) specifically silences DG cultured hippocampal neurons,...
Abstract Nuclear speckles, also known as interchromatin granule clusters (IGCs), are subnuclear domains highly enriched in proteins involved transcription and mRNA metabolism and, until recently, have been regarded primarily their storage modification hubs. However, several recent studies on non-neuronal cell types indicate that nuclear speckles may directly contribute to gene expression some of the active genes shown associate with these structures. Neuronal activity is one key...
ABSTRACT Serotonin regulates multiple physiological and pathological processes in the brain, including mood cognition. The serotonin receptors 5-HT1AR (also known as HTR1A) 5-HT7R HTR7) have emerged key players stress-related disorders, particularly depression. These can form heterodimers, which influence their functions. Here, we explored developmental dynamics of expression validated heterodimerization levels brain control stressed mice. In animals, found that there was an increase over...
The neuromuscular junctions (NMJs) connect muscle fibers with motor neurons and enable the coordinated contraction of skeletal muscles. dystrophin-associated glycoprotein complex (DGC) is an essential component postsynaptic machinery NMJ important for maintenance structural integrity. To identify novel proteins that are organization, we performed a mass spectrometry-based screen interactors α-dystrobrevin 1, one components DGC. guanidine nucleotide exchange factor Arhgef5 was found to be 1...
Abstract Dystroglycan (DG) is a cell membrane protein that binds to the extracellular matrix in various mammalian tissues. The function of DG has been well defined embryonic development as proper migration differentiated neuroblasts central nervous system (CNS). Although known be target for metalloproteinase-9 (MMP-9), cleaved response enhanced synaptic activity, role structural remodeling dendritic spines still unknown. Here, we report first time deletion rat hippocampal cultures causes...
The complexity of the depressive symptoms observed in humans makes modeling behavior rodents challenging. Here, we present a highly reproducible protocol to generate mouse models that mimic several aspects depression, namely anhedonia and loss motivation. We describe acclimatization animals baseline determination, followed by chronic unpredictable stress (CUS) induce anhedonic resilient behaviors. can mice at roughly equal frequencies, providing reliable model for translational research. For...
In the search for new options pharmacological treatment of major depressive disorder, compounds with a rapid onset action and high efficacy but lacking psychotomimetic effect are particular interest. present study, we evaluated antidepressant potential NitroSynapsin (NS) at behavioural, structural, functional levels. NS is memantine derivative dual allosteric N-methyl-d-aspartate receptors (NMDAR) antagonist using targeted delivery by aminoadamantane warhead nitro group to inhibitory redox...