Department of Experimental Neuroendocrinology
Scope of research:
New evidences for a role of mGluR7 in astrocyte survival: Possible implications for neuroprotection.
Danuta Jantas, Tomasz Lech, Sławomir Gołda, Andrzej Pilc, Władysław Lasoń
Neuropharmacology, S0028-3908(18)30585-9 10.1016/j.neuropharm.2018.08.035
Targeting the NLRP3 Inflammasome-Related Pathways via Tianeptine Treatment-Suppressed Microglia Polarization to the M1 Phenotype in Lipopolysaccharide-Stimulated Cultures.
Joanna Ślusarczyk, Ewa Trojan, Katarzyna Głombik, Anna Piotrowska, Bogusława Budziszewska, Marta Kubera, Katarzyna Popiołek-Barczyk, Władysław Lasoń, Joanna Mika, Agnieszka Basta-Kaim
International journal of molecular sciences, E1965 10.3390/ijms19071965
An endogenous and ectopic expression of metabotropic glutamate receptor 8 (mGluR8) inhibits proliferation and increases chemosensitivity of human neuroblastoma and glioma cells.
Danuta Jantas, Beata Grygier, Sławomir Gołda, Jakub Chwastek, Justyna Zatorska, Magdalena Tertil
Cancer letters, S0304-3835(18)30400-2 10.1016/j.canlet.2018.06.004
The reduced level of growth factors in an animal model of depression is accompanied by regulated necrosis in the frontal cortex but not in the hippocampus.
Mateusz Kucharczyk, Anna Kurek, Bartosz Pomierny, Jan Detka, Mariusz Papp, Katarzyna Tota, Bogusława Budziszewska
Psychoneuroendocrinology, S0306-4530(17)31488-9 10.1016/j.psyneuen.2018.05.008
Allosteric and Orthosteric Activators of mGluR8 differentially affect the Chemotherapeutic-induced Human Neuroblastoma SH-SY5Y Cell Damage: The Impact of Cell Differentiation State.
Danuta Jantas, Beata Grygier, Justyna Zatorska, Władysław Lasoń
Basic & clinical pharmacology & toxicology, 10.1111/bcpt.13041
The Effects of Exposure to Mephedrone During Adolescence on Brain Neurotransmission and Neurotoxicity in Adult Rats.
Katarzyna Kamińska, Karolina Noworyta-Sokołowska, Anna Górska, Joanna Rzemieniec, Agnieszka Wnuk, Adam Wojtas, Grzegorz Kreiner, Małgorzata Kajta, Krystyna Gołembiowska
Neurotoxicity research, 10.1007/s12640-018-9908-0
Prenatal exposure to benzophenone-3 (BP-3) induces apoptosis, disrupts estrogen receptor expression and alters the epigenetic status of mouse neurons.
Agnieszka Wnuk, Joanna Rzemieniec, Ewa Litwa, Władysław Lasoń, Małgorzata Kajta
The Journal of steroid biochemistry and molecular biology, S0960-0760(18)30103-1 10.1016/j.jsbmb.2018.04.016
Triclosan-Evoked Neurotoxicity Involves NMDAR Subunits with the Specific Role of GluN2A in Caspase-3-Dependent Apoptosis.
Konrad A Szychowski, Agnieszka Wnuk, Joanna Rzemieniec, Małgorzata Kajta, Teresa Leszczyńska, Anna K Wójtowicz
Molecular neurobiology, 10.1007/s12035-018-1083-z
The effect of dermal benzophenone-2 administration on immune system activity, hypothalamic-pituitary-thyroid axis activity and hematological parameters in male Wistar rats.
Żaneta Broniowska, Joanna Ślusarczyk, Beata Starek-Świechowicz, Ewa Trojan, Bartosz Pomierny, Weronika Krzyżanowska, Agnieszka Basta-Kaim, Bogusława Budziszewska
Toxicology, S0300-483X(18)30050-7 10.1016/j.tox.2018.04.002
Regulators of glucocorticoid receptor function in an animal model of depression and obesity.
Anna Kurek, Katarzyna Głombik, Jan Detka, Agnieszka Basta-Kaim, Marta Kubera, Władysław Lasoń, Bogusława Budziszewska
Journal of neuroendocrinology, 10.1111/jne.12591
Mitochondrial proteomics investigation of frontal cortex in an animal model of depression: Focus on chronic antidepressant drugs treatment.
Katarzyna Głombik, Aneta Stachowicz, Ewa Trojan, Joanna Ślusarczyk, Maciej Suski, Katarzyna Chamera, Katarzyna Kotarska, Rafał Olszanecki, Agnieszka Basta-Kaim
Pharmacological reports : PR, S1734-1140(17)30491-7 10.1016/j.pharep.2017.11.016
Steroid and Xenobiotic Receptor Signalling in Apoptosis and Autophagy of the Nervous System.
Agnieszka Wnuk, Małgorzata Kajta
International journal of molecular sciences, E2394 10.3390/ijms18112394
Novel ureidopropanamide based N-formyl peptide receptor 2 (FPR2) agonists with potential application for central nervous system disorders characterized by neuroinflammation.
Madia Letizia Stama, Joanna Ślusarczyk, Enza Lacivita, Liliya N Kirpotina, Igor A Schepetkin, Katarzyna Chamera, Chiara Riganti, Roberto Perrone, Mark T Quinn, Agnieszka Basta-Kaim, Marcello Leopoldo
European journal of medicinal chemistry, S0223-5234(17)30737-7 10.1016/j.ejmech.2017.09.023
The Modulatory Properties of Chronic Antidepressant Drugs Treatment on the Brain Chemokine - Chemokine Receptor Network: A Molecular Study in an Animal Model of Depression.
Ewa Trojan, Joanna Ślusarczyk, Katarzyna Chamera, Katarzyna Kotarska, Katarzyna Głombik, Marta Kubera, Agnieszka Basta-Kaim
Frontiers in pharmacology, 10.3389/fphar.2017.00779
Bazedoxifene and raloxifene protect neocortical neurons undergoing hypoxia via targeting ERα and PPAR-γ.
J Rzemieniec, E Litwa, A Wnuk, W Lason, M Kajta
Molecular and cellular endocrinology, S0303-7207(17)30450-1 10.1016/j.mce.2017.08.014
The role of the inflammasome NLRP3 in the mechanisms of antidepressant drugs action - studies in the animal model of depression, Ewa Trojan, PhD
The aim of the project is to determine whether the enhanced inflammatory activation of microglia cells from animals subjected to a model of depression is connected with disturbances of the amount and function of NLRP3 complexes. The studies will be conducted in vivo in 3 months old males, offspring of control and stressed dams before and after chronic, 14-day administration of antidepressant drugs with different mechanism of action. Simultaneously, the studies will be conducted in vitro on primary microglial cultures derived from the cerebral cortex of 1-2-day-old Sprague-Dawley rats from the control group and from an animal model of depression both under basal conditions and after an additional activation by the bacterial endotoxin (lipopolysaccharide, LPS).
Molecular mechanism of action of antidepressant drugs in the in vitro model of contact allergy in the human cell line HaCat and mouse dendritic precursor JAWSII cells, Katarzyna Curzytek, MSc
The aim of the project is to determine the mechanism of action of antidepressant drugs with different profiles of action engaged in the inhibition of contact hypersensitivity response in two cell lines: the human keratinocyte HaCaT and the mouse dendritic precursor JAWSII. Antidepressants, such as fluoxetine and desipramine proved effective in suppressing contact hypersensitivity (classical example of cell-mediated immune response) in a murine model of contact hypersensitivity. The used antidepressants not only strongly inhibit contact sensitization, but also have shown immunomodulatory effects, but their molecular mechanism of action in inhibition of contact allergy, remains unknown. It is postulated that the use of cellular model for the study of the efficacy of antidepressant drugs in reducing inflammatory response, will contribute to broadening of our knowledge of the intracellular mechanisms of action of these drugs.
Neurotoxic effects of benzophenone-3 : the role of estrogen receptors and retinoid X receptor alpha., Agnieszka Wnuk, MSc
Benzophenone-3 (BP-3) is one of the most commonly used UV filters, which is demonstrated as a hormonally active substance in vitro studies. However, data on the effects of benzophenone-3 on the nervous system are scarce. Especially little is known about the impact of BP-3 on individual receptors that are strongly associated with brain development. The main idea of this project is to investigate the neurotoxic effect of benzophenone-3 on neuronal cells and to establish molecular basis of its activity, with particular emphasis on estrogen receptors and retinoid X receptor alpha. Basic research hypothesis assumes that benzophenone-3 induces a neurotoxic effect and initiates the apoptotic process in the neuronal cells simultaneously modifying activity of the estrogen receptors (ERα, ERβ, GPR30) and retinoid X receptor alpha (RXRα) as well as makes changes in DNA methylation profile.
The impact of maternal diabetes on inflammasome NLRP3 activation in the offspring brain, Katarzyna Głombik, PhD
The aim of the project is to determine potential functional changes in the inflammasome NLRP3, considered to be a sensor of metabolic changes in offspring of dams with experimentally induced diabetes using organotypic cultures of the hippocampus. It is known that fetal exposure to maternal diabetes can activate inflammatory processes and can increase many times a risk of type 2 diabetes in the offspring. However, the mechanism of these disturbances remains unknown. The most recent reports suggest the role of changes in the inflammasome NLPR3 complex in this mechanism which can lead to aggravation of inflammatory processes and disturbances in glucose metabolism or resistance to insulin, thus predisposing offspring to development of type 2 diabetes. Sparse for now studies underlined the significance of disturbances in homeostasis due to pathological factors, like maternal diabetes, for instance, in the modulation of central nervous system function both in young and adult offspring. The studies within this research project will answer the question whether the function of the inflammasome NLRP3 is disturbed in the hippocampus of young offspring of diabetic dams. Thus, they will elucidate causes of the changed inflammatory activation, which can lead to an increased susceptibility to metabolic disturbances of the brain and type 2 diabetes in adulthood. What is more, they can help to discover a new target for anti-diabetic drugs with anti-inflammatory potential and can contribute to a better understanding of the mechanisms of their action.
The influence of glucagon-like peptie-1 receptor agaonists on regulation of coticotropin-releasing hormone gene promoter activity UMO-2012/07/N/NZ7/04394, Jan Detka, PhD
The aim of the project is to determine the effect of glucagon-like peptide-1 receptor (GLP-1R) agonists, used to treat type 2 diabetes on the regulation of corticoliberin (CRH) gene expression. Many reports have indicated a distinct role of GLP-1 as a brain modulator of neuroendocrine processes, emphasizing its implication in hypothalamic-pituitary-adrenal (HPA) axis activation. Considering that chronic HPA axis activation is thought to be an important factor in the pathogenesis of depression which can also stimulate type 2 diabetes development in some depressed patients, it is necessary to better understand GLP-1 involvement in hormonal regulation in the organism and its action in the hypothalamus. Numerous papers suggest GLP-1 involvement in the activation of hypothalamic paraventricular neurons and most recent reports indicate its influence on CRH expression in transiently transfected neuronal cell line. However, so far the effect of GLP-1 on CRH gene expression was not studied in terms protein kinase A activation (main pathway of CRH activation in stress) or attenuation of CRH gene activity by glucocorticoids. It is also undetermined if the potential effect of GLP-1 in the hypothalamus depends on insulin, as well as nobody studied the cellular mechanisms, involved in the following processes.
The role of glucocorticoids in the regulation of neurodegenerative process, Anna Kurek, MSc
Glucocorticoids can produce either protective or neurodegenerative effects, depending on the concentration and duration of action. Experimental data have indicated that long-lastingly increased glucocorticoid level can contribute to neurodegenerative changes observed in depression and after cerebral stroke. However, in opposite to in vivo studies, in a majority of in vitro experiments, neurotoxic action of glucocorticoids was observed only after application of their very high doses. Since in vivo investigations have demonstrated that glucocorticoids influence many types of nervous system cells (neurons, astrocytes, microglia), it appears that the lack of junctions between different cells can be one of causes of their weak cytotoxic effect in in vitro studies, conducted most often in neuronal cultures. Moreover, in a few studies on organotypic cultures carried out so far, the cultures were initiated from tissues collected from control animals while HPA axis activity and strength of glucocorticoid action in adults largely depends on factors acting in perinatal period. The aim of the proposed experiments is to examine a potential, cytotoxic action of corticosterone and its interaction with glutamate in organptypic cultures of the hippocampus obtained from the prenatally stress-exposed animals.
We assume that prenatal stress which changes expression of many factors affecting the function of glucocorticoid and NMDA receptors and glutamate level will alter also the effect of corticosterone on neurodegenerative/neuroprotective processes in the hippocampus. Determination of the effect and mechanism of action of corticosterone added to culture medium on markers of cell damage in organotypic cultures of hippocampi from control and prenatally stressed animals (an animal model of depression) will allow for answering the question whether the changes triggered by prenatally elevated glucocorticoids will sensitize the tissue to damaging factors acting in adulthood.
The study on the neuroprotective potential of metabotropic glutamate group II and III receptors in in vitro and in vivo apoptosis models., Danuta Jantas, PhD
Grant KBN nr N N405 611638; Principial Investigator
The study on the role of metabotropic glutamate receptor subtype 8 (mGluR8) in cancer cells - potential target for new anticancer drugs., Danuta Jantas, PhD
Grant NCN OPUS 3 2012/05/B/NZ3/00452; Principial Investigator
Stipends START 2018 granted by The Foundation for Polish Science (FNP) stipends for the young scientists, Agnieszka Wnuk, MSc
Saturday, 26 May 2018
, Katarzyna Głombik, PhD
Saturday, 21 May 2016
, Joanna Rzemieniec, PhD
Monday, 30 November -0001
, Joanna Rzemieniec, PhD
Monday, 30 November -0001
- colorometric evaluation of macrophage activity
- eleveted zero test
- eozynophilic test
- flow cytometry
- forced swim test
- Griess test
- hypoosmotic test
- immobilisation stress
- immune cells tissue cultures
- in vitro transfection
- LDH test
- liquid chromatography
- locomotor activity
- mammalian cells tissue cultures
- MTT test
- novel obiect recognition
- open field test
- organotypic cultures
- prepulse inhibition
- primary cultures
- protein fractioning
- protein microarrays
- radiologand binding
- Real Time PCR
- sucrose preference test
- tail suspension test
- tissue cultures with stable expressing genes encoding selected proteins
- Western Blot
- Alzheimer disease
- behavioural analysis
- Bipolar disorder
- estrogen receptors
- fluorescent microscopy
- G-protein coupled receptors
- gene expression
- glutamatergic receptors
- immobilization stress
- immune system
- metabotropic glutamate receptors
- mitochondrial proteins
- molecular biology
- neuroendocrine regulation
- neurotrophic factors
- NMDA receptor
- Parkinson's disease
- signaling proteins
- stem cells
- xenobiotic receptors