Laboratory of Neuropharmacology and Epigenetics

Scientific profile

  • About department
  • Employees

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.
Małgorzata Kajta

Professor Małgorzata Kajta, dr hab.

Head

+48 12 6623235
room 52 A

Pracownicy zakładu

Agnieszka Wnuk, dr hab.

+48 12 6623338
room 341

Karolina Przepiórska-Drońska, mgr

+48 12 6623339
room 128

Katarzyna Tomczyk

room 128

Andrzej Łach, mgr inż.

+48 12 6623339
room 128

Bernadeta Pietrzak-Wawrzyńska, mgr

+48 12 6623339
room 128

Achievements

  • Publications
  • Grants
  • Awards

Grant

Selective PPARγ modulation by amorfrutin B as a novel therapeutic approach to chemotherapy-induced damage to mammalian brain cells, Bernadeta Pietrzak-Wawrzyńska, MSc NCN PRELUDIUM 22 Grant; 2023/49/N/NZ7/03640 The Scientific Supervisor of the project: Professor Małgorzata Kajta, PhD

Bernadeta A. Pietrzak-Wawrzyńska, MSc,

Grant

Selective modulation of PPARγ signaling as a new therapeutic strategy for Alzheimer’s disease NCN PRELUDIUM Grant; 2022/45/N/NZ7/01418; 2023-2026. Ongoing. The Scientific Supervisor of the project: Professor Małgorzata Kajta, PhD

Karolina Przepiórska-Drońska, MSc

Grant

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, PhD

Grant

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

Grant

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

Grant

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

Grant

Neurotoxic effects of benzophenone-3 : the role of estrogen receptors and retinoid X receptor alpha The Scientific Supervisor of the project: Professor Małgorzata Kajta, PhD

Agnieszka Wnuk, PhD

Grant

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 The Scientific Supervisor of the project: Professor Małgorzata Kajta, PhD

Ewa Litwa

Grant

Effect of selective estrogen receptor modulators and aromatic hydrocarbon receptors on hypoxia / ischemia-induced apoptosis of neuronal cells The Scientific Supervisor of the project: Professor Małgorzata Kajta, PhD

Joanna Rzemieniec

Grant

Neuroprotective capacities of phytoestrogens in neurodevelopmental models of hypoxia and excitotoxicity

Professor Małgorzata Kajta, PhD

Grant

Task 2.3: The role of estrogen receptor, aryl hydrocarbon receptor, and retinoid receptor signaling pathways in pathomechanisms of depression

Professor Małgorzata Kajta, PhD

Grant

A role of dioxins and aryl hydrocarbon receptor in apoptosis of neuronal cells: mechanisms and protective strategies

Professor Małgorzata Kajta, PhD

Award

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-Drońska, MSc

Award

Team Award of the V Faculty of Medical Sciences of the Polish Academy of Sciences for a series of publications

Agnieszka Wnuk, PhD

Award

A Team Award of the V Faculty of Medical Sciences of the Polish Academy of Sciences for a series of publications

Professor Małgorzata Kajta, PhD

Award

Stipends START 2018 granted by The Foundation for Polish Science (FNP) stipends for the young scientists

Agnieszka Wnuk, PhD

Award

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

Award

A Team Award of the V Faculty of Medical Sciences of the Polish Academy of Sciences for a series of publications

Professor Małgorzata Kajta, PhD

Neuroprotective action of raloxifene against hypoxia-induced damage in mouse hippocampal cells depends on ERα but not ERβ or GPR30 signalling

Rzemieniec, J., Litwa, E., Wnuk, A., Lason, W., Gołas, A., Krzeptowski, W., Kajta, M.

DOI: 10.1016/j.jsbmb.2014.05.005

Enhanced delivery of daidzein into fibroblasts and neuronal cells with cationic derivatives of gamma-cyclodextrin for the control of cellular glycosaminoglycans

Kamiński, K., Kujdowicz, M., Kajta, M., Nowakowska, M., Szczubiałka, K.

DOI: 10.1016/j.ejpb.2015.02.002

Neuroprotective action of raloxifene against hypoxia-induced damage in mouse hippocampal cells depends on ERα but not ERβ or GPR30 signalling

Rzemieniec, J., Litwa, E., Wnuk, A., Lason, W., Gołas, A., Krzeptowski, W., Kajta, M.

DOI: 10.1016/j.jsbmb.2014.05.005

Salsolinol, an Endogenous Compound Triggers a Two-Phase Opposing Action in the Central Nervous System

Możdżeń, E., Kajta, M., Wąsik, A., Lenda, T., Antkiewicz-Michaluk, L.

DOI: 10.1007/s12640-014-9511-y

Isomer-nonspecific action of dichlorodiphenyltrichloroethane on aryl hydrocarbon receptor and G-protein-coupled receptor 30 intracellular signaling in apoptotic neuronal cells

Kajta, M., Litwa, E., Rzemieniec, J., Wnuk, A., Lason, W., Zelek-Molik, A., Nalepa, I., Grzegorzewska-Hiczwa, M., Tokarski, K., Golas, A., Guzik, E., Grochowalski, A., Szychowski, K.A., Wojtowicz, A.K.

DOI: 10.1016/j.mce.2014.05.008

Apoptotic and neurotoxic actions of 4-para-nonylphenol are accompanied by activation of retinoid X receptor and impairment of classical estrogen receptor signaling

Litwa, E., Rzemieniec, J., Wnuk, A., Lason, W., Krzeptowski, W., Kajta, M.

DOI: 10.1016/j.jsbmb.2014.07.014

1-benzyl-1,2,3,4-tetrahydroisoquinoline, an endogenous neurotoxic compound, disturbs the behavioral and biochemical effects of L-DOPA: In vivo and ex vivo studies in the rat

Wa̧sik, A., Romańska, I., Michaluk, J., Kajta, M., Antkiewicz-Michaluk, L.

DOI: 10.1007/s12640-014-9476-x

The key involvement of estrogen receptor β and G-protein-coupled receptor 30 in the neuroprotective action of daidzein

Kajta, M., Rzemieniec, J., Litwa, E., Lason, W., Lenartowicz, M., Krzeptowski, W., Wojtowicz, A.K.

DOI: 10.1016/j.neuroscience.2013.02.005

Aryl hydrocarbon receptor-mediated apoptosis of neuronal cells: A possible interaction with estrogen receptor signaling

Kajta, M., Wójtowicz, A.K., Maćkowiak, M., Lasoń, W.

DOI: 10.1016/j.neuroscience.2008.10.045

Neuroprotective effects of neuropeptide Y-Y2 and Y5 receptor agonists in vitro and in vivo

Śmiałowska, M., Domin, H., Zieba, B., Koźniewska, E., Michalik, R., Piotrowski, P., Kajta, M.

DOI: 10.1016/j.npep.2009.02.002

Head

Professor Małgorzata Kajta, dr hab.

+48 12 6623235
room 52 A

See also