Department of Experimental Neuroendocrinology
Scope of research:
Role of Chronic Administration of Antidepressant Drugs in the Prenatal Stress-Evoked Inflammatory Response in the Brain of Adult Offspring Rats: Involvement of the NLRP3 Inflammasome-Related Pathway.
Ewa Trojan, Katarzyna Chamera, Natalia Bryniarska, Katarzyna Kotarska, Monika Leśkiewicz, Magdalena Regulska, Agnieszka Basta-Kaim
Molecular neurobiology, 10.1007/s12035-018-1458-1
Prenatal Exposure to Benzophenone-3 Impairs Autophagy, Disrupts RXRs/PPARγ Signaling, and Alters Epigenetic and Post-Translational Statuses in Brain Neurons.
Agnieszka Wnuk, Joanna Rzemieniec, Jakub Staroń, Ewa Litwa, Władysław Lasoń, Andrzej Bojarski, Małgorzata Kajta
Molecular neurobiology, 10.1007/s12035-018-1401-5
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
Triclocarban Disrupts the Epigenetic Status of Neuronal Cells and Induces AHR/CAR-Mediated Apoptosis.
M Kajta, A Wnuk, J Rzemieniec, W Lason, M Mackowiak, E Chwastek, M Staniszewska, I Nehring, A K Wojtowicz
Molecular neurobiology, 10.1007/s12035-018-1285-4
Effects of exposure to 5-MeO-DIPT during adolescence on brain neurotransmission and neurotoxicity in adult rats.
Karolina Noworyta-Sokołowska, Katarzyna Kamińska, Joanna Rzemieniec, Agnieszka Wnuk, Jakub Wojcieszak, Anna Maria Górska, Grzegorz Kreiner, Małgorzata Kajta, Krystyna Gołembiowska
Forensic toxicology, 10.1007/s11419-018-0433-x
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
- Kajta M, Rzemieniec J, Rużyłło W. In search of new therapeutic strategies for the treatment of hypoxia-ischemia-induced brain damages. An article in Polish. NAUKA, 2016, 3:55-73
- Kajta M. How hormonally active environmental contaminants affect the brain? An article in Polish. Wszechświat, 2012, 113:10-13.
- Kajta M. Molecular mechanisms of estrogen action in the central nervous system. Chapter in the script: Cellular signaling pathways. Edited by I. Nalepa. XXI Zimowa Szkoła Instytutu Farmakologii PAN. Mogilany, 2004, 61-69.
- Kajta M. Neuronal cell cultures. An article in Polish. Chapter XVII in the book: Cell and Tissue Cultures. Edited by S. Stokłosowa. PWN, Warszawa, 2004, 277-290.
Neurodevelopmental pathomechanisms of triclocarban-, and Dichlorodiphenyldichloroethylene (DDE)-induced effects: the roles of apoptosis and autophagy as well as the receptor signaling for estrogens, aryl hydrocarbons and androstane. NCN OPUS Grant; 2015/19/B/NZ7/02449; 2016-2019. Ongoing. Principal Investigator of the project: Małgorzata Kajta, Małgorzata Kajta, PhD
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).
Neurotoxic effects of benzophenone-3 : the role of estrogen receptors and retinoid X receptor alpha., Agnieszka Wnuk, PhD
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.
Neurotoxic effects of benzophenone-3: the roles of estrogen receptors and the retinoid X receptor alpha. NCN PRELUDIUM Grant; 2014/13/N/NZ4/04845; 2015-2018. Principal Investigator of the project: Agnieszka Wnuk. The scientific supervisor of the project: Małgorzata Kajta, Małgorzata Kajta, PhD
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 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
PRELUDIUM 3: 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.Grant implemented in the years: 2013-2016
Impact of endocrine-disrupting compound - 4-para-nonylphenol – on toxic effects mediated by xenobiotic receptors PXR and CAR during neural development in vitro and in vivo. NCN PRELUDIUM Grant; 2011/01/N/NZ4/04950; 2011-2014. Principal Investigator of the project: Ewa Litwa. The scientific supervisor of the project: Małgorzata Kajta, Małgorzata Kajta, PhD
The scientific supervisor of the project: Impact of selective modulators of estrogen receptors and aryl hydrocarbon receptor on hypoxia/ischemia-induced apoptosis of neuronal cells. NCN PRELUDIUM Grant; 2011/01/N/NZ3/04786; 2011-2014. Principal Investigator: Joanna Rzemieniec,, Małgorzata Kajta, PhD
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
Neuroprotective capacities of phytoestrogens in neurodevelopmental models of hypoxia and excitotoxicity. MNiSW Grant; N N401 572138; 2010-2013. Principal Investigator of the project: Małgorzata Kajta , Małgorzata Kajta, PhD
Task 2.3: The role of estrogen receptor, aryl hydrocarbon receptor, and retinoid receptor signaling pathways in pathomechanisms of depression. The project Depression-Mechanisms-Therapies (DeMeTer) co-funded by the EU’s European Regional Development Fund, as part of the ‘Innovative Economy: 2007-2013 National Cohesion Strategy’ Operational Programme. POIG.01.01.02-12-004/09 Grant; 2010-2014. Principal Investigator of the task 2.3: Małgorzata Kajta, Małgorzata Kajta, PhD
A role of dioxins and aryl hydrocarbon receptor in apoptosis of neuronal cells: mechanisms and protective strategies; MEiN Grant; 2P05A 123 30; 2006 2009. Principal Invetigator of the project: Małgorzata Kajta, Małgorzata Kajta, PhD
OPUS 5: The role of chemokines in the pathogenesis of depression and molecular mechanism of action of antidepressants, grant completed (2014-2017), Professor Agnieszka Basta - Kaim, PhD
The aim of the project was a determination in adult - 3-month-old male Sprague-Dawley rats in brain structures (frontal cortex, hippocampus) of expression and level of selected chemokines (fractalkine/CX3CL1 [neurotactin NTN] and MCP-1/CCL2 [monocyte chemotactic protein 1/chemokine CC motif ligand 2] and SDF-1/CXCL12 [stromal cell-derived factor 1]) and their receptors in an animal model of depression. At the same time, in adult animals, the influence of antidepressants with different mechanisms of action (desipramine, fluoxetine, tianeptine, venlafaxine) on the chemokine receptor system was examined. Previous studies had shown that prenatal stress is a risk factor for the development of depression later in life (at the age of 3 months), therefore in the project research in young animals was conducted, using ex vivo technique - organotypic hippocampal culture, which is a unique research model allowing to maintain natural connections between the immune and neuroendocrine system, cytoarchitecture and functional neuron - glia interactions, which allowed to examine the molecular mechanism of participation of chemokines and their receptors in the genesis of changes observed at the age of 3 months.
Team Award of the V Faculty of Medical Sciences of the Polish Academy of Sciences, Agnieszka Wnuk, PhD
Thursday, 22 November 2018
A Team Award of the V Faculty of Medical Sciences of the Polish Academy of Sciences for a series of 5 publications entitled "Identification of new molecular mechanisms involving the estrogen receptors and the receptors for xenobiotics in neuroprotection and neurotoxicity". Warsaw, 22.11.2018., Małgorzata Kajta, PhD
Thursday, 22 November 2018
The scholarship of the President of the Polish Academy of Sciences for outstanding scientific achievements of participants of PhD studies conducted by Institutes of Polish Academy of Sciences, Katarzyna Chamera, MSc
Tuesday, 20 November 2018
Stipends START 2018 granted by The Foundation for Polish Science (FNP) stipends for the young scientists, Agnieszka Wnuk, PhD
Saturday, 26 May 2018
, Katarzyna Głombik, PhD
Saturday, 21 May 2016
J. J. Supniewski Foundation award for scientific achievements. Krakow, 2004, Małgorzata Kajta, PhD
Wednesday, 25 February 2004
, 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