Laboratory of Molecular Neuroendocrinology


Research profile

Research topics are related to civilization diseases, such as strokes and the nervous system disorders resulting from exposures to environmental pollution. The team conducts research that fits into the search for new therapies that protect the brain from hypoxia. The team also attempts to understand the molecular, including epigenetic, mechanisms of action of hormonally active substances, which are present in the environment (DDT, DDE, benzophenone-3, triclocarban), and link them with the etiology of the nervous system diseases.

The team's research includes both the subject of neuroprotection, especially in the context of strokes, as well as the subject of developmental toxicity consisting in the disruption of homeostasis of nerve cells and the entire organism by exposures to environmental factors such as pesticides, chemical UV filters or biocides.

The Laboratory of Molecular Neuroendocrinology focuses on the neuroprotective potential of phytoestrogens (genistein, daidzein) as well as selective modulators of estrogen receptors (raloxifene, bazedoxifene) and the aryl hydrocarbon receptor (3,3'-diindolylmethane) in models of hypoxia/ischemia and excitotoxicity. Research topics also include molecular mechanisms through which hormonally active environmental pollutants affect mammalian nerve cells.

 

The most important discoveries

The team pointed to the aryl hydrocarbon receptor (AhR) for the first time as a possible target to improve the pharmacotherapy of brain hypoxia. Inhibition of the AhR receptor pathway has proven to be the primary mechanism of the protective action of 3,3'-diindolylmethane (DIM) in hypoxic/ischemic neuronal cells.

The team was the first to demonstrate that selective estrogen receptor modulators (SERMs) protect nerve cells against hypoxia not only via the estrogen receptor α (ERα), but also via the peroxisome proliferator-activated receptor γ (PPARγ), as demonstrated by the effects of raloxifene and bazedoxifene.

The team was the first to prove that the exposures of embryonic neuronal cells to environmental pollutants, i.e., DDT pesticide and its metabolite DDE, chemical UV filter - benzophenone-3 or biocide - triclocarban, disrupt the pathways of estrogen receptors (ERα/ESR1, ERβ/ESR2, GPR30/GPER1) and xenobiotic receptors (AhR, CAR, RXR, PXR) as well as change the epigenetic status of mammalian brain nerve cells.

The team showed first that prenatal exposure to DDT pesticide may be the cause of depressive-like disorder. This effect is specific for the p,p'-DDT isomer and is associated with a decrease in estrogen ERα and GPR30 receptors (currently ESR1 and GPER1), hypermethylation of Esr1 and Gper1 genes, and global DNA hypomethylation in mouse brain.

The team showed first that prenatal exposure to benzophenone-3 intensifies apoptosis, impairs autophagy, and interferes with the expression and function of estrogen receptors (ERα/ESR1, ERβ/ESR2, GPR30/GPER1), retinoid X receptors (RXRα, RXRβ, RXRγ) and the peroxisome proliferator-activated receptor γ (PPARγ), and changes the epigenetic status of mouse brain nerve cells. Microarray analyses showed that prenatal exposure to benzophenone-3 also interferes with the expression of specific miRNAs involved in neurogenesis and neurotransmission or in the progression of neurological diseases.

 

Research methods

  • Primary cultures of mouse brain neuronal cells carried out in distributed and organotype systems
  • Cultures of stem neural cells and astrocytes
  • Models of hypoxia, ischemia and excitotoxicity in neuronal cells in vitro and in vivo
  • Assessment of cytotoxicity by measuring the release of lactate dehydrogenase (LDH), MTT
  • Assessment of cell survival by staining with calcein AM
  • Determination of oxidative stress markers
  • Examination of apoptosis by measuring membrane mitochondrial potential and activity of caspases, as well as staining of apoptotic bodies with Hoechst dye 33342
  • Examination of the autophagy process by measuring the level of autophagosomes and specific markers of this process
  • Measurement of gene expression by qPCR and microarrays
  • Measurement of protein expression by ELISA and western blot
  • Immunofluorescence detection of receptors in nerve cells
  • Epigenetic analyses of nerve cells
  • Silencing of gene expression using specific siRNAs
  • Measurement of CYP1A1 cytochrome catalytic activity
  • Basic behavioral tests: FST, TST, NOR


Keywords

apoptosis, aryl hydrocarbon receptor (AhR), asphyxia, autophagy, bazedoxifene, benzophenone-3, constitutive androstane receptor (CAR), 3,3’-diindolylmethane (DIM), daidzein, DDE, DDT, DNA methylation, epigenetics, estrogen receptors (ERs/ESR; GPR30/GPER1), excitotoxicity, genistein, hypoxia, ischemia, microarrays, molecular biology, neuroprotection, neurotoxicity, pesticides, primary neuronal cell cultures, raloxifene, retinoid X receptors (RXRs), peroxisome proliferator-activated receptors (PPARs), phytoestrogens, selective aryl hydrocarbon receptor modulators (SAhRMs), selective estrogen receptor modulators (SERMs), stroke, triclocarban, xenobiotic receptors
More publications
  • Synthesis, crystal structure and selected properties of a group of new peroxomolybdates

    Adrianna Sławińska, Paweł Serda, Katarzyna Pamin, Jan Połtowicz, Wiesław Łasocha

    Polyhedron, Volume 121 (2017) 191-198

    https://doi.org/10.1016/j.poly.2016.09.062

  • In search of new therapeutic strategies for the treatment of hypoxia-ischemia-induced brain damages. An article in Polish.

    NAUKA, 2016, 3:55-73. Kajta M, Rzemieniec J, Rużyłło W.

  • How hormonally active environmental contaminants affect the brain? An article in Polish. Wszechświat, 2012, 113:10-13. Kajta M.
  • Molecular mechanisms of estrogen action in the central nervous system. An article in Polish. Chapter in the script: Cellular signaling pathways. Edited by I. Nalepa. XXI Zimowa Szkoła Instytutu Farmakologii PAN. Mogilany, 2004, 61-69. Kajta M.
  • Neuronal cell cultures. An article in Polish. Chapter XVII in the book: Cell and Tissue Cultures. Edited by S. Stokłosowa. PWN, Warszawa, 2004, 277-290. Kajta M.
  • In search of new therapeutic strategies for the treatment of hypoxia-ischemia-induced brain damages. An article in Polish. NAUKA, 2016, 3:55-73. Kajta M, Rzemieniec J, Rużyłło W.


More publications
  • Searching for effective strategies to protect neuronal cells against hypoxia and ischemia: Identification of neuroprotective mechanisms of the new ligands of AhR and PPARg in experimental models of stroke, Professor Małgorzata Kajta, PhD

    NCN OPUS Grant; 2018/31/B/NZ7/01815; 2019-2022. Ongoing.

    Principal Investigator of the project: Małgorzata Kajta


  • Neurodevelopmental pathomechanisms of triclocarban-, and Dichlorodiphenyldichloroethylene (DDE)-induced effects: the roles of apoptosis and autophagy as well as the receptor signaling for estrogens, aryl hydrocarbons and androstane. , Professor Małgorzata Kajta, PhD

    NCN OPUS Grant; 2015/19/B/NZ7/02449; 2016-2019.

    Principal Investigator of the project: Małgorzata Kajta


  • Neurotoxic effects of benzophenone-3 : the role of estrogen receptors and retinoid X receptor alpha., Agnieszka Wnuk, PhD

    NCN PRELUDIUM Grant; 2014/13/N/NZ4/04845; 2015-2018

    Principal Investigator of the project: Agnieszka Wnuk, PhD

    The Scientific Supervisor of the project: Małgorzata Kajta, PhD

  • Impact of endocrine-disrupting compound - 4-para-nonylphenol – on toxic effects mediated by xenobiotic receptors PXR and CAR during neural development in vitro and in vivo. , Professor Małgorzata Kajta, PhD

    NCN PRELUDIUM Grant; 2011/01/N/NZ4/04950; 2011-2014.

    Principal Investigator of the project: Ewa Litwa

    The scientific supervisor of the project: Małgorzata Kajta

  • Impact of selective modulators of estrogen receptors and aryl hydrocarbon receptor on hypoxia/ischemia-induced apoptosis of neuronal cells, Joanna Rzemieniec, PhD

    NCN PRELUDIUM Grant; 2011/01/N/NZ3/04786; 2011-2014.

    Principal Investigator: Joanna Rzemieniec

    The scientific supervisor of the project: Małgorzata Kajta

  • Neuroprotective capacities of phytoestrogens in neurodevelopmental models of hypoxia and excitotoxicity. , Professor Małgorzata Kajta, PhD

    MNiSW Grant; N N401 572138; 2010-2013.

    Principal Investigator of the project: Małgorzata Kajta

  • Task 2.3: The role of estrogen receptor, aryl hydrocarbon receptor, and retinoid receptor signaling pathways in pathomechanisms of depression. , Professor Małgorzata Kajta, PhD

    The project Depression-Mechanisms-Therapies (DeMeTer) co-funded by the EU’s  European Regional Development Fund, as part of the ‘Innovative Economy: 2007-2013 National Cohesion Strategy’ Operational Programme. POIG.01.01.02-12-004/09 Grant; 2010-2014.

    Principal Investigator of the task 2.3: Małgorzata Kajta

  • A role of dioxins and aryl hydrocarbon receptor in apoptosis of neuronal cells: mechanisms and protective strategies., Professor Małgorzata Kajta, PhD

    MEiN Grant; 2P05A 123 30; 2006 2009.

    Principal Invetigator of the project: Małgorzata Kajta

more_grants
  • Team Award of the V Faculty of Medical Sciences of the Polish Academy of Sciences for a series of 5 publications entitled "Identification of new molecular mechanisms involving the estrogen receptors and the receptors for xenobiotics in neuroprotection and neurotoxicity"., Agnieszka Wnuk, PhD
    Thursday, 22 November 2018
  • A Team Award of the V Faculty of Medical Sciences of the Polish Academy of Sciences for a series of 5 publications entitled "Identification of new molecular mechanisms involving the estrogen receptors and the receptors for xenobiotics in neuroprotection and neurotoxicity". , Professor Małgorzata Kajta, PhD
    Thursday, 22 November 2018
  • A Team Award of the V Faculty of Medical Sciences of the Polish Academy of Sciences for a series of 5 publications entitled "Identification of new molecular mechanisms involving the estrogen receptors and the receptors for xenobiotics in neuroprotection and neurotoxicity", Joanna Rzemieniec, PhD
    Thursday, 22 November 2018
  • Second place in the competition for a popular science article "Can broccoli protect us against the consequences of a stroke?" - organizer of the competition Directorate of the Institute of Pharmacology PAS in Kraków, Joanna Rzemieniec, PhD
    Friday, 5 October 2018
  • 3rd Central European Biomedical Congress Award for the Best Presentation entiled “Neuroprotective capacity of DIM against ischemia involves inhibition of AhR, but not ERα signaling”, Joanna Rzemieniec, PhD
    Tuesday, 18 September 2018
  • Stipends START 2018 granted by The Foundation for Polish Science (FNP) stipends for the young scientists, Agnieszka Wnuk, PhD
    Saturday, 26 May 2018
  • The second place in the competition for a popular-science article "Sunscreen cream - friend or foe?"- the Organizer: Directorate of the IF PAS in Krakow , Agnieszka Wnuk, PhD
    Wednesday, 15 November 2017
  • Scholarship of the President of the Polish Academy of Sciences, Joanna Rzemieniec, PhD
    Wednesday, 7 December 2016
  • L’Oréal-UNESCO For Women in Science Fellowship, Joanna Rzemieniec, PhD
    Thursday, 24 November 2016
  • Junior Travel Grant of 2016 of the European Stroke Conference and European Stroke Foundation , Joanna Rzemieniec, PhD
    Friday, 15 April 2016
  • J. J. Supniewski Foundation award for scientific achievements., Professor Małgorzata Kajta, PhD
    Wednesday, 25 February 2004
more_awards