Laboratory of Immunoendocrinology
The Laboratory of Immunoendocrinology is a part of the Department of Experimental Neuroendocrinology.
The laboratory consists of three research teams:
Professor Agnieszka Basta-Kaim, Magdalena Szuster PhD, Ewa Trojan PhD, Natalia Bryniarska MSc, Katarzyna Chamera MSc
The main research interests of this team pertrain to the role of chemokines and their receptors in the pathogenesis of central nervous system diseases, particularly depression, schizophrenia, Alzheimer's disease and brain ischemia. In our research we focus on understanding the role of immunocompetent brain cells activation in the development of depressive disorders, the contribution of neuronal-microglial interactions in neurodevelopmental models of schizophrenia, as well as the mechanisms of action of drugs used in the therapy of these diseases. New trends in our research include the role of neuroimmune and metabolic disorders in the epigenetic mechanisms in senile dementia associated with type 2 diabetes and the dysfunctions observed in the course of Alzheimer's disease. The research profile of our team includes also the search for new formyl receptor agonists as a potential new strategy for quenching the inflammatory processes (including alternative activation) in the course of central nervous system diseases. We conduct comprehensive experimental studies using animal models of brain diseases, including transgenic animals, methods for organotypic cell cultures and primary brain cell cultures (microglia, astrocytes). We also use chemical and molecular biology techniques.
Our team is currently working on three projects funded by the National Science Center (NCN): HARMONIA 9, OPUS 10 and PRELUDIUM 9, as well as two international grants: the American Alzheimer's Association project and Joint Programme - Neurodegenerative Disease Research (JPND), co-funded by the EU HORIZON 2020.
Professor Bogusława Budziszewska, Katarzyna Głombik PhD, Jan Detka PhD, Anna Kurek MSc
The research interests of the team focus on the brain carbohydrate metabolism in animal models of depression and metabolic diseases coexisting with depression such as diabetes, obesity, hyperthyroidism and hypothyroidism. Glucose is the main source of energy for the central nervous system, it is also essential to maintain the activity of synapses, neurotransmitters synthesis and as a source of NADPH, which protects cells against oxidative stress. Brain metabolism is disrupted in a number of pathological conditions, such as neurodegenerative diseases, mental disorders and cancer.
In our experiments, we use selectively bred Wistar-Kyoto rats as an animal model of endogenous depression as well as models based on chronic stress procedures (e.g. prenatal stress and chronic mild stress). Our research methodology includes both behavioral experiments and biochemical and molecular techniques that allow us to measure the activity and expression of enzymes involved in brain energy metabolism (glycolysis, Krebs cycle, respiratory chain), the quantitative evaluation of the components involved in these processes (glucose and its metabolites, transporters, enzymes) and the activity of hormones involved in the regulation of glucose metabolism, such as insulin and incretins.
Professor Marta Kubera, Katarzyna Curzytek MSc
Our research interests include studies on the role of cytokines (interleukins, chemokines) and neurotrophic factors and their receptors in the pathogenesis of central nervous system diseases, especially depression and in the mechanisms of action of antidepressant drugs. Our research is also aimed at understanding the role of the neuroimmunoendocrine component in the individual sensitivity to stress and cognitive biases. We also study the effects of antidepressants on the course of neoplastic process and contact hypersensitivity response. In our research, we use animal models of diseases as well as cell lines: HaCaT, YAWS II, PC12, SH-SY5Y, B16F10, MADB 106.
The N-Formyl Peptide Receptor 2 (FPR2) Agonist MR-39 Improves Ex Vivo and In Vivo Amyloid Beta (1-42)-Induced Neuroinflammation in Mouse Models of Alzheimer's Disease.
Ewa Trojan, Kinga Tylek, Nicole Schröder, Iris Kahl, Lars-Ove Brandenburg, Margherita Mastromarino, Marcello Leopoldo, Agnieszka Basta-Kaim, Enza Lacivita
Molecular neurobiology, 10.1007/s12035-021-02543-2
The N-Formyl Peptide Receptor 2 (FPR2) Agonist MR-39 Exhibits Anti-Inflammatory Activity in LPS-Stimulated Organotypic Hippocampal Cultures.
Ewa Trojan, Kinga Tylek, Monika Leśkiewicz, Władysław Lasoń, Lars-Ove Brandenburg, Marcello Leopoldo, Enza Lacivita, Agnieszka Basta-Kaim
Cells, 1524 10.3390/cells10061524
Formyl peptide receptor 2, as an important target for ligands triggering the inflammatory response regulation: a link to brain pathology.
Kinga Tylek, Ewa Trojan, Magdalena Regulska, Enza Lacivita, Marcello Leopoldo, Agnieszka Basta-Kaim
Pharmacological reports : PR, 10.1007/s43440-021-00271-x
Glutathione Deficiency during Early Postnatal Development Causes Schizophrenia-Like Symptoms and a Reduction in BDNF Levels in the Cortex and Hippocampus of Adult Sprague-Dawley Rats.
Marta Anna Lech, Monika Leśkiewicz, Kinga Kamińska, Zofia Rogóż, Elżbieta Lorenc-Koci
International journal of molecular sciences, 6171 10.3390/ijms22126171
Venlafaxine and L-Thyroxine Treatment Combination: Impact on Metabolic and Synaptic Plasticity Changes in an Animal Model of Coexisting Depression and Hypothyroidism.
Katarzyna Głombik, Jan Detka, Bogusława Budziszewska
Cells, 1394 10.3390/cells10061394
Shedding light on the role of CX3CR1 in the pathogenesis of schizophrenia.
Katarzyna Chamera, Magdalena Szuster-Głuszczak, Agnieszka Basta-Kaim
Pharmacological reports : PR, 10.1007/s43440-021-00269-5
Insights into a possible role of glucagon-like peptide-1 receptor agonists in the treatment of depression.
Jan Detka, Katarzyna Głombik
Pharmacological reports : PR, 10.1007/s43440-021-00274-8
Mitochondria-targeting therapeutic strategies in the treatment of depression.
Katarzyna Głombik, Bogusława Budziszewska, Agnieszka Basta-Kaim
Mitochondrion, S1567-7249(21)00038-6 10.1016/j.mito.2021.03.006
Stiffening of DU145 prostate cancer cells driven by actin filaments - microtubule crosstalk conferring resistance to microtubule-targeting drugs.
Andrzej Kubiak, Matteo Chighizola, Carsten Schulte, Natalia Bryniarska, Julita Wesołowska, Maciej Pudełek, Małgorzata Lasota, Damian Ryszawy, Agnieszka Basta-Kaim, Piotr Laidler, Alessandro Podestà, Małgorzata Lekka
Contribution of Hypothyroidism to Cognitive Impairment and Hippocampal Synaptic Plasticity Regulation in an Animal Model of Depression.
Katarzyna Głombik, Jan Detka, Bartosz Bobula, Joanna Bąk, Magdalena Kusek, Krzysztof Tokarski, Bogusława Budziszewska
International journal of molecular sciences, 1599 10.3390/ijms22041599
Role of Polyinosinic:Polycytidylic Acid-Induced Maternal Immune Activation and Subsequent Immune Challenge in the Behaviour and Microglial Cell Trajectory in Adult Offspring: A Study of the Neurodevelopmental Model of Schizophrenia.
Katarzyna Chamera, Ewa Trojan, Katarzyna Kotarska, Magdalena Szuster-Głuszczak, Natalia Bryniarska, Kinga Tylek, Agnieszka Basta-Kaim
International journal of molecular sciences, 1558 10.3390/ijms22041558
Effects of L-DOPA on Gene Expression in the Frontal Cortex of Rats with Unilateral Lesions of Midbrain Dopaminergic Neurons.
Anna Radlicka, Kinga Kamińska, Malgorzata Borczyk, Marcin Piechota, Michał Korostyński, Joanna Pera, Elżbieta Lorenc-Koci, Jan Rodriguez Parkitna
eNeuro, ENEURO.0234-20.2020 10.1523/ENEURO.0234-20.2020
Evaluation of Cysteine Metabolism in the Rat Liver and Kidney Following Intravenous Cocaine Administration and Abstinence.
Danuta Kowalczyk-Pachel, Małgorzata Iciek, Anna Bilska-Wilkosz, Magdalena Górny, Joanna Jastrzębska, Kinga Kamińska, Paulina Dudzik, Małgorzata Filip, Elżbieta Lorenc-Koci
Antioxidants (Basel, Switzerland), E74 10.3390/antiox10010074
Impaired Brain Energy Metabolism: Involvement in Depression and Hypothyroidism.
Katarzyna Głombik, Jan Detka, Anna Kurek, Bogusława Budziszewska
Frontiers in neuroscience, 10.3389/fnins.2020.586939
Multilineage Differentiation Potential of Human Dental Pulp Stem Cells-Impact of 3D and Hypoxic Environment on Osteogenesis In Vitro.
Anna Labedz-Maslowska, Natalia Bryniarska, Andrzej Kubiak, Tomasz Kaczmarzyk, Malgorzata Sekula-Stryjewska, Sylwia Noga, Dariusz Boruczkowski, Zbigniew Madeja, Ewa Zuba-Surma
International journal of molecular sciences, E6172 10.3390/ijms21176172
Application of dental pulp stem cells in neural tissue regeneration
PRELUDIUM 18: Evaluation of molecular mechanisms of neuroprotective action of dental pulp stromal cells in an ex vivo organotypic model of ischemia, Natalia Bryniarska-Kubiak, MSc
Principal investigator: Natalia Bryniarska
Financed by the National Science Center (NCN)
, Katarzyna Głombik, 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).
PRLEUDIUM 7: 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, PhD
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.
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.
, Katarzyna Głombik, PhD
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.
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.
OPUS 10: The role of the neuron-microglia CX3CL1-CX3CR1 and CD200-CD200R protein systems in molecular mechanisms of antipsychotic drug actions: in vivo and in vitro study in the neurodevelopmental models of schizophrenia, grant in progress (2016- ), Professor Agnieszka Basta - Kaim, PhD
Recent results indicate the importance of certain proteins, including fractalkine (CX3CL1) and surface antigens, such as CD200, and their receptors (CX3CR1, CD200R) in controlling and maintaining neuronal-microglial communication. The key biological significance of these mechanisms is due to the specific location of the ligand (CX3CL1, CD200) mainly on neurons, and receptors (CX3CR1, CD200R) on microglial cells.
Therefore, the aim of the project is to determine the role of selected systems of neuronal and microglial proteins: fractalkine (CX3CL1) and CD200 antigen and their receptors (CX3CR1, CD200R) not only in the pathogenesis of schizophrenia but also in the mechanisms of action of antipsychotics.
The implementation of the project will help to explain the role of disorders of the studied protein systems in brain ontogeny in the pathomechanisms of schizophrenia in an adulthood, and on the other hand, gives an opportunity to discover new potential points of grip for antipsychotic drugs.
Furthermore, the susceptibility of CX3CL1-CX3CR1 and CD200-CD200R systems to modulation by atypical drugs may give a new, practical tool to increase the efficacy of pharmacotherapy for schizophrenia, especially its negative and cognitive symptoms.
HARMONIA 9: Modulation of inflammatory processes using new agonists of the formyl peptide receptors ALX/FPR2 as a new therapeutic strategy of depression, grant in progess (2018- ), Professor Agnieszka Basta - Kaim, PhD
One of the factors that conducive to the development of depression is the severe and prolonged inflammation associated with the dysfunction of endogenous processes controlling its resolution. Clinical data show that anti-inflammatory drugs have a pronounced antidepressant effect, however, due to the risk of serious side effects resulting, among others, from a total inhibition of inflammatory reactions in the organism, their use in the pharmacotherapy of depression is severely limited. Therefore, the aim of this project is to examine the possibility of applying a new treatment strategy for depression, which consists of strengthening the endogenous mechanisms of resolution the harmful inflammatory reaction by stimulating FPR2 peptide receptors, while maintaining normal life-saving pro-inflammatory functions. Research is carried out on three levels: in vitro in primary microglia cultures, ex vivo in organotypic hippocampal cultures and in vivo in adult rats, representing two different animal depression models (prenatal stress and one-time administration of lipopolysaccharide). Strengthening the resolution of the inflammation is carried out with the use of new urea-derived FPR2 receptor agonists. During the project implementation, the effect of new FPR2 receptor agonists on cell death/survival processes, NO levels, iNOS activity, gene expression and levels of selected cytokines and pro-inflammatory profile chemokines will be assessed. In addition, the molecular mechanism of action of the studied agonists and the role of FPR2 receptor expression on microglial cells in the anti-inflammatory effects of the agonists studied will be examined. Moreover, the use of two animal models will allow the assessment of the effects of new FPR2 receptor agonists on the behavior of animals, as well as on levels of markers of M1 and M2 phenotypes of microglia and pro-and anti-inflammatory factors in the hippocampus and frontal cortex of their brains.
Joint Programme – Neurodegenerative Disease Research (JPND) grant: EpiAD: Effect of early and adult-life stress on the brain epigenome: relevance for the occurrence of Alzheimer’s Disease and Diabetes-related dementia, grant in progress (2018- ), Professor Agnieszka Basta - Kaim, PhD
The aim of the project is to assess the effect of prenatal stress on the development of senile dementia in the course of Alzheimer's disease and type 2 diabetes and to determine whether the effect of prenatal stress is modulated by the action of additional stressors occurring in adulthood. In addition, in the project, an examining whether prenatal stress and/or stress factor (a high-fat diet) in adulthood lead to disturbances in the insulin pathway in the brain that contribute to the development of Alzheimer's disease and dementia associated with type 2 diabetes is planned.
Behavioral and biochemical studies planned as part of the project will be conducted using APPNL-F/NL-F transgenic mice, which constitute a unique model of Alzheimer's disease because they show many disturbances typical for the disease (among others: amyloid plaque deposition, loss of synaptic connections). Furthermore, C57BL/6 mice will also be used, which will be fed a high-fat diet to induce type 2 diabetes.
The project of Alzheimer's Association: Drug Development of Pro-resolving ALX/FPR2 Agonists for Alzheimer’s Disease, grant in progress (2018- ), Professor Agnieszka Basta - Kaim, PhD
The aim of the project is to evaluate the potential efficacy of new urea-derived agonists of the FPR2 receptor as a tool for the resolution of inflammatory processes. The transgenic knock-out FPR2-/- animals are used to implement the assumptions of the project. Research includes the synthesis and multifaceted chemical verification of new urea-derived agonists of FPR2, post in vivo studies (organotypic cultures) and in vivo (behavioral tests). The correlation of results obtained post in vivo with in vivo results will allow the selection of the most promising new FPR2 antagonists as potential compounds for the modulation of inflammatory processes, by a resolution of them in conditions of inflammation and Alzheimer's disease coexistence.
Scholarship of the President of the Polish Academy of Sciences, Natalia Bryniarska-Kubiak, MSc
Monday, 30 November 2020
Scholarship for the best PhD students at the Maj Institute of Pharmacology, Polish Academy of Sciences (2020/2021), Natalia Bryniarska-Kubiak, MSc
Friday, 13 November 2020
Laureate of the competition organized by "Pharmacological reports" and director of May Institute of Pharmacology Polish Academy of Sciences for the best draft of review article, Natalia Bryniarska-Kubiak, MSc
Tuesday, 10 November 2020
Scholarship of the Minister of Science and Higher Education for outstanding young scientists, Katarzyna Głombik, PhD
Monday, 15 June 2020
FENS Grant and Voucher Programme grant for participating in the FENS 2020 Virtual Forum, 11-15.07.2020, Katarzyna Chamera, PhD
Friday, 15 May 2020
The best work in the Pharmacy and Pharmacology session during the 10th National Conference on Advence in Biomedical Research in Warsaw, Natalia Bryniarska-Kubiak, MSc
Saturday, 30 November 2019
The main prize of Professor Kazimierz Ostrowski for the best work presented during the 10th National Conference on Advences in Biomedical Research in Warsaw, Natalia Bryniarska-Kubiak, MSc
Saturday, 30 November 2019
Neuron of The Audience: Best Poster on 9th Annual Conference Aspects of Neuroscience in Warsaw, Natalia Bryniarska-Kubiak, MSc
Sunday, 24 November 2019
Scholarship for the best PhD students at the Maj Institute of Pharmacology Polish Academy of Sciences (2019/2020), Natalia Bryniarska-Kubiak, MSc
Thursday, 7 November 2019
3rd place in the competition for a popular science article for young scientists of the Polish Academy of Sciences, Natalia Bryniarska-Kubiak, MSc
Friday, 27 September 2019
The doctoral scholarship (ETIUDA 7) financed by the National Science Centre, Poland, Katarzyna Chamera, PhD
Wednesday, 31 July 2019
The travel grant award for the 2019 ISN-ASN Meeting, Montreal, Canada, 4-8.08.2019, Katarzyna Chamera, PhD
Tuesday, 26 March 2019
The travel grant award from NAWA's PROM project for the XIV European Meeting on Glial Cells in Health and Disease, Porto, Portugal, 10-13.07.2019, Katarzyna Chamera, PhD
Tuesday, 29 January 2019
, Ewa Trojan, PhD
Tuesday, 29 January 2019
, Katarzyna Głombik, PhD
Thursday, 20 December 2018
- colorometric evaluation of macrophage activity
- eleveted zero test
- eozynophilic test
- 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
- model of trangenic knock out
- Morris water maze
- MTT test
- novel obiect recognition
- open field test
- organotypic cultures
- prepulse inhibition
- 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
- behavioural analysis
- Bipolar disorder
- confocal microscopy
- fluorescent microscopy
- G-protein coupled receptors
- immobilization stress
- immune system
- mitochondrial proteins
- molecular biology
- neuroendocrine regulation
- signaling proteins
- stem cells