Department of Experimental Neuroendocrinology


Scope of research:

  • effects of antidepressant and antipsychotic drugs on endocrinological and immunological systems;
  • effects of antidepressants on the immune response;
  • effects of antidepressants on tumor growth;
  • estrogen interactions with internal and external apoptotic pathways;
  • impact of estrogens and selective estrogen receptor modulators (SERMs) on excitatory amino acid-, proinflammatory cytokine-, and dioxin-induced neuronal cell damage;
  • intracellular mechanisms of apoptotic processes in neuronal cells;
  • molecular interaction of antidepressants and drugs of abuse with corticosteroid receptors;
  • molecular interactions of psychotropic drugs with glucocorticoid receptors and the corticotropin-releasing hormone gene;
  • role of thyrotropin-releasing hormone and steroids in excitotoxicity, seizures and apoptosis;
  • apoptotic effects of dioxins and AhR in neuronal cells;
  • neuroprotective action of phytoestrogens in neurodevelopmental models of hypoxia and excitotoxicity;
  • effects of endocrine disruptors on neuronal development;
  • influence of antidepressants on apoptotic processes;
  • effect of metabotropic glutamatergic group II and III ligands on neuronal apoptosis


Methods:

Behavioural:

- excitatory amino acid-induced seizures;
- LPS-induced depression-like and schizophrenia-like syndromes in animals;
- prenatal restraint stress in the rat - animal model of depression.

Surgical:
- experimental skin transplantation;
- splenectomy; adrenalectomy; ovariectomy;
- induction of a systemic or a regional graft-versus-host reaction;
- stereotaxic brain surgery.

Biochemical:
- primary neuronal cell cultures (striatal, neocortical, hippocampal, cerebellar cells);
- cell line cultures (PC12, neuro-2A, NG108-15, SH-SY5Y, SK-N-SH);
- immune cell cultures;
- transient and stable transfection of adherent mammalian cells;
- assay of reporter gene activity in transfected cell extracts;
- lactate dehydrogenase assay;
- MAP-2 and GFAP immunostainings;
- assessment of the mitochondrial dehydrogenase activity;
- caspase-3 activity assay;
- DNA-laddering;
- calcein/ethidium homodimer-1 test;
- nitrite assay;
- estimation of the metabolic activity of macrophages;
- Hoechst 33342 and calcein AM double staining;
- measurement of neurotransmitter uptake;
- determination of neurotransmitter release in vitro;
- electrophoresis of proteins and the Western blot analysis;
- radioligand receptor binding techniques;
- assay of protein kinases;
- in situ hybridization analysis of mRNA;
- receptor autoradiography;
- ELISA;
- siRNA gene silencing;
- double immunostainings.


International cooperation:

- the Institute of Cognition and Information of the Nijmegen University (the Netherlands) -- involvement of steroids in the regulation of epileptic activity in WAG/Rij rats;

- the Institute of Neurobiology, Bulgarian Academy of Sciences (Bulgaria) - ROS in the effects of anti-inflammatory and anti-depressant drugs;

- the Clinical Research Centre for Mental Health in Antwerp (Belgium) - examination of the effect of antidepressants and serotonin receptors ligands on cytokine production by human immunocytes;

- the University of Basque Country in Bilbao (Spain) - the effect of antidepressant drugs on tumor growth;

- the Institute of Neuroanatomy, RWTH Aachen – University Clinic (Germany) - studies on the interaction between estrogens and cytokines in neurodegenerative processes.

More publications
  • Aneta Fraczek-Szczypta, Danuta Jantas, Filip Ciepiela, Justyna Grzonka. Graphene oxide-conductive polymer nanocomposite coatings obtained by the EPD method as substrates for neurite outgrowth. Diamond & Related Materials 102 (2020) 107663.


  • Application of dental pulp stem cells in neural tissue regeneration


  • Marek Piotrowski, Danuta Jantas, Monika Leśkiewicz, Krzysztof Szczepanowicz, Piotr Warszyński, Władysław Lasoń. Polyelectrolyte-coated nanocapsules containing cyclosporine A protect neuronal-like cells against oxidative stress-induced cell damage. Colloids and Surfaces A: Physicochemical and Engineering Aspects Volume 555, 20 October 2018, Pages 264-269.


  • Aneta Fraczek-Szczypta, Danuta Jantas, Filip Ciepiela, Justyna Grzonka, Andrzej Bernasike, Mateusz Marzec. Carbon nanomaterials coatings – Properties and influence on nerve cells response. Diamond and Related Materials Volume 84, April 2018, Pages 127–140.


  • M. Szczęch, K. Szczepanowicz, D. Jantas, M. Piotrowski, A. Kida, W. Lasoń, P. Warszyński. Neuroprotective action of undecylenic acid (UDA) encapsulated into PCL nanocarriers. Colloids and Surfaces A 532 (2017) 41–47.
  • Marek Piotrowski, Krzysztof Szczepanowicz, Danuta Jantas, Monika Leskiewicz, Władysław Lason, Piotr Warszynski. Emulsion-core and polyelectrolyte-shell nanocapsules: biocompatibility and neuroprotection against SH-SY5Y cells. J Nanopart Res (2013) 15:1-12.


  • Gręda A., Jantas D. Dysfunkcje mitochondriów w chorobach neurodegeneracyjnych: potencjalny punkt uchwytu dla leków neuroprotekcyjnych. Postępy Biologii Komórki, TOM 39 2012 NR 3 (321–344). Review in Polish.


  • Danuta Jantas. Thyreoliberin (TRH) – the regulatory neuropeptide of CNS homeostasis. Advances in Cell Biology 2010, 2:138-152.
  • Jantas D. Cell-Based Systems of Depression: An Overview. In: Herbal Medicine in Depression. Ed. Clara Grosso. Springer, Switzerland 2016, p. 75-117. DOI 10.1007/978-3-319-14021-6.
  • Lasoń W., Jantas D. Rola epigenetyki w mechanizmach i leczeniu padaczki (The role of epigenetics in pathomechanisms and epilepsy treatment). Article In Polish. Epileptologia 2009, 17:113-122.
  • Jantas-Skotniczna D. Estrogeny – nie tylko hormony płciowe (Rola estrogenów w Ośrodkowym Układzie Nerwowym). [Estrogens – not only sexual hormons (The role of estrogens In Central Nervous System)]. Wszechświat, 2004; 105: 191-194. Review. Polish.
  • Jantas-Skotniczna D. ALS – cichy zabójca (Nasze szanse w walce ze stwardnieniem bocznym zanikowym). [ALS – the sileni killer (Our chances to combat Amyotropic Lateral Sclerosis)]. Wszechświat, 2006; 107: 31-33. Review. Polish.
More publications
  • 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.
  • 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
  • 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
  • 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.
more_grants
  • 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
more_awards
Head

Professor Agnieszka Basta - Kaim, PhD

Phone number: +48 12 6623273
E-mail: basta@if-pan.krakow.pl