Professor Agnieszka Basta - Kaim, PhD
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
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
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
OPUS 5: The role of chemokines in the pathogenesis of depression and molecular mechanism of action of antidepressants, grant completed (2014-2017)
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- )
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- )
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- )
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- )
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.
- Katedra Farmakologii CM UJ (Kraków)
- Katedra Neurologii CM UJ (Kraków)
- Zakład Biochemii Toksykologicznej, Wydział Farmaceutyczny CM UJ (Kraków)
- Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Fédérale Lausanne (Lozanna, Szwajcaria)
- Center for Molecular Neurobiology Hamburg (Hamburg, Niemcy)
- Centro de Biología Molecular Severo Ochoa, Universidad Autonoma de Madrid (Madryt, Hiszpania)
- Department of Neurology, University Hospital La Paz (Madryt, Hiszpania)
- Dipartimento di Farmacia – Scienze del Farmaco, Universita degli Studi di Bari Aldo Moro (Bari, Włochy)
- Institute for Laboratory Animal Science, University Hospital RWTH (Aachen, Niemcy)