Laboratory of Immunoendocrinology


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  • 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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