Laboratory of Immunoendocrinology


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  • 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.

  • 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.

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  • , Katarzyna Głombik, PhD
    Saturday, 21 May 2016
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