Laboratory of Neuropharmacology and Epigenetics


Laboratory of Neuropharmacology and Epigenetics

 

Historical view

The Laboratory of Neuropharmacology and Epigenetics was established on April 23, 2021 as part of the Department of Pharmacology at the Maj Institute of Pharmacology of the Polish Academy of Sciences.

The laboratory was established as a result of the transformation of the Laboratory of Molecular Neuroendocrinology, operating since August 7, 2018.

The laboratory is one of the five innovative research laboratories created as part of the project entitled "Modernization of the building and research infrastructure of the Institute of Pharmacology of the Polish Academy of Sciences in Krakow in order to create innovative laboratories for brain research" implemented in the years 2009-2013.

The funds for the establishment of the Laboratory came from the Innovative Economy Operational Program (2.1. Development of centers with high research potential, European Regional Development Fund, 2007-2013 perspective).

The idea of ​​establishing the Laboratory appeared in response to the competition entitled "Idea for a new laboratory" announced by the Director of the Institute of Pharmacology of the Polish Academy of Sciences, prof. Krzysztof Wędzony in 2009.

 

Research profile

Searching for substances with neuroprotective potential constituting the basis of new therapies for stroke, perinatal asphyxia and Alzheimer's disease.

Identifying molecular mechanisms of neurotoxicity caused by exposures of cells or animals to hormonally active substances present in the environment and their roles in etiology of nervous system diseases.

 

Tests and models

Primary cultures of rodent brain neurons carried out in dispersed and organotypic systems

Cultures of nerve stem cells and astrocytes

Cultures of human neurons derived from induced pluripotent stem cells (iPSCs)

Cellular and animal models of strokes, perinatal asphyxia and Alzheimer's disease

 

The most important discoveries

Selective modulation of the PPARγ receptor by amorfrutin B or the membrane fraction of estrogen receptors by PaPE-1 produces a neuroprotective effect in cellular models of cerebral hypoxia and ischemia. Moreover, PaPE-1 protects nerve cells from the toxic effects of amyloid-β

The aryl hydrocarbon receptor (AhR) can be a target for drugs to improve the pharmacotherapy of cerebral hypoxia, as demonstrated by both in vitro (neuronal cells exposed to hypoxia / ischemia) and in vivo (rats exposed perinatally to asphyxia) studies.

Prenatal exposure to the biocide - triclocarban impairs the signaling pathways of the ERα receptor (now ESR1), disrupts the expression of genes involved in neurogenesis and neurotransmission, and changes the epigenetic status in the brains of postnatal mice in a sex-specific manner.

Prenatal exposure to the DDT pesticide may cause depressive-like disorders, which is associated with a reduction in the levels of estrogen receptors ERα and GPR30 (now ESR1 and GPER1), hypermethylation of the genes encoding them, and global DNA hypomethylation in the mouse brain.

Exposures of embryonic neuronal cells to environmental pollutants, i.e., the pesticide DDT and its metabolite DDE, the chemical UV filter - benzophenone-3 or the biocide - triclocarban, disrupt the signaling pathways of estrogen receptors and xenobiotic receptors, and change the epigenetic status of mammalian brain cells.

 

Research methods

Assessment of cytotoxicity and cell survival, incl. measurement of lactate dehydrogenase (LDH) release, staining with calcein AM, NeuroFluor ™ NeuO.

Determination of markers of oxidative stress with the use of 2 ', 7'-dichlorodihydrofluorescein diacetate (H2DCFDA).

Study of the processes of apoptosis and autophagy by measuring the level of specific markers (including caspases, membrane mitochondrial potential, apoptotic bodies, autophagosomes).

 Molecular analyzes incl. measurement of gene expression by qPCR and microarrays, measurement of protein expression by ELISA and western blot methods, silencing of gene expression using specific siRNAs.

Epigenetic analyzes, incl. measurement of DNA methylation, both global and specific genes, measurement of the activity of enzymes involved in histone modification (HAT, HDAC, sirtuin), miRNA expression specific for central nervous system diseases.

Immunofluorescence detection of specific proteins using confocal microscopy.

Blood-brain barrier permeation testing using an artificial system containing nerve cells, astrocytes and endothelial cells.

 

Keywords

apoptosis, aryl hydrocarbon receptor (AhR), asphyxia, autophagy, bazedoxifene, benzophenone-3, 3,3'-diindolomethane (DIM), daidzein, DDE, DDT, DNA methylation, epigenetics, estrogen receptors (ER / ESR; GPR30 / GPER1), excitotoxicity, genistein, hypoxia, ischemia, microarrays, miRNA, molecular biology, neuroprotection, neurotoxicity, pesticides, peroxisome proliferator activated receptors (PPAR), phytoestrogens, primary neuronal cultures, raloxifene, retinoid X receptors (RXRs), selective estrogen receptor modulators (SERMs), selective aryl hydrocarbon receptor modulators (SAhRMs), siRNA, stroke, triclocarban, xenobiotic receptors

More publications
  • A popular-science article "From birth to old age - amorfrutin B in neuroprotection" Karolina Przepiórska

    Link to the article

  • Popular science article "Sunscreen cream - friend or foe?" Agnieszka Wnuk

    Link to the article

  • 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.
More publications
  • , Agnieszka Wnuk, PhD

    New post-treatment strategy against stroke and perinatal asphyxia – a novel approach based on a selective activation of membrane estrogen receptors mERα and mERβ, Agnieszka Wnuk, 

    NCN SONATA Grant; 2021/43/D/NZ7/00633; 2022-2025.

    Principal Investigator of the grant:  Agnieszka Wnuk, PhD





  • Selective activation of non-nuclear Estrogen Receptor signaling with PaPE-1 as a novel therapeutic approach for sporadic Alzheimer’s Disease, Professor Małgorzata Kajta, PhD

    NCN OPUS Grant; 2020/39/B/NZ7/00974; 2021-2024. Ongoing.

    Principal Investigator of the grant: Małgorzata Kajta

  • 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 grant: 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 grant: 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, MSc

    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 grant: Ewa Litwa

    The scientific supervisor of the grant: Małgorzata Kajta

  • Effect of selective estrogen receptor modulators and aromatic hydrocarbon receptors on hypoxia / ischemia-induced apoptosis of neuronal cells, Professor Małgorzata Kajta, PhD

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

    Principal Investigator of the grant: Joanna Rzemieniec

    The Scientific Supervisor of the grant: 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 grant: 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; 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 grant: Małgorzata Kajta

more_grants
  • The first place in the competition for a popular-science article "From birth to old age - amorfrutin B in neuroprotection" - the Organizer: board of Directors of the Maj Institute of Pharmacology of the Polish Academy of Sciences., Karolina Przepiórska, MSc
    Thursday, 30 September 2021
  • 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
  • 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
  • J. J. Supniewski Foundation award for scientific achievements., Professor Małgorzata Kajta, PhD
    Wednesday, 25 February 2004
more_awards