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
  • https://www.sciencedirect.com/science/article/pii/S0925963517305678

  • M. Szczęch, K.Szczepanowicz, D.Jantas, M.Piotrowski, A.Kida, W.Lasoń, P.Warszyńsk. Neuroprotective action of undecylenic acid (UDA) encapsulated into PCL nanocarriers. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2017, 532: 41-47


  • https://link.springer.com/article/10.1007/s11051-013-2035-1

  • Jantas D. Thyreoliberin (TRH) – the regulatory neuropeptide of CNS homeostasis. Advances in Cell Biology 2010, 2(1):138-152.


More publications
  • 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.
  • Neurotoxic effects of benzophenone-3 : the role of estrogen receptors and retinoid X receptor alpha., Agnieszka Wnuk, MSc
    Benzophenone-3 (BP-3) is one of the most commonly used UV filters, which is demonstrated as a hormonally active substance in vitro studies. However, data on the effects of benzophenone-3 on the nervous system are scarce. Especially little is known about the impact of BP-3 on individual receptors that are strongly associated with brain development. The main idea of this project is to investigate the neurotoxic effect of benzophenone-3 on neuronal cells and to establish molecular basis of its activity, with particular emphasis on estrogen receptors and retinoid X receptor alpha. Basic research hypothesis assumes that benzophenone-3 induces a neurotoxic effect and initiates the apoptotic process in the neuronal cells simultaneously modifying activity of the estrogen receptors (ERα, ERβ, GPR30) and retinoid X receptor alpha (RXRα) as well as makes changes in DNA methylation profile.
  • The impact of maternal diabetes on inflammasome NLRP3 activation in the offspring brain, 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, MSc
    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.
  • , Ewa Trojan, MSc

more_grants
  • , Katarzyna Głombik, PhD
    Saturday, 21 May 2016
  • , Joanna Rzemieniec, PhD
    Monday, 30 November -0001
  • , Joanna Rzemieniec, PhD
    Monday, 30 November -0001
more_awards
Head

Professor Władysław Lasoń, PhD

Phone number: +48 12 6623296
E-mail: lason@if-pan.krakow.pl