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 a result of the transformation of the Laboratory of Molecular Neuroendocrinology, which had been operating since August 7, 2018.
The Laboratory is one of five innovative research laboratories established 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 research laboratories for brain research" carried out in 2009-2013. 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, perspective 2007-2013).
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. The initiator of the establishment of the Laboratory and its current Head is Prof. Małgorzata Kajta.
The dynamic
development of the Laboratory has created an environment conducive to
professional development, as evidenced by the academic degrees and titles
obtained. Since 2018, 4 employees have been promoted, obtaining: the academic
degree of doctor of medical sciences in the discipline of medical biology
(2018), the academic title of professor of medical sciences (2019), the
academic degree of doctor habilitated in the field of medical sciences and
health sciences in the discipline of medical sciences (2024), and the academic
degree of doctor in the field of medical sciences and health sciences in the
discipline of medical sciences (2025).
Research profile
Scientific research focuses on lifestyle/non-communicable diseases, especially strokes and Alzheimer's disease, as well as on disorders of the nervous system associated with long-term exposure to environmental pollutants. Initially, the main area of research was the molecular mechanisms of neurotoxicity caused by exposure of cells or animals to hormonally active substances present in the environment and their roles in etiology of nervous system diseases. The latest research focuses on the search for substances with neuroprotective potential, which may form the basis of new therapies for strokes and Alzheimer's disease.
Models
• Primary cultures of rodent brain neurons carried out in dispersed and organotypic systems
• Cultures of neural stem cells and microglia
• Cultures of human neurons derived from induced pluripotent stem cells (iPSCs)
• Cellular and animal models of stroke, perinatal asphyxia, and Alzheimer's disease
Key findings
• Selective modulator of the membrane fraction of estrogen receptors (mERα, mERβ), which is PaPE-1, induces a neuroprotective effect in cellular models of Alzheimer's disease. The mechanism of action of PaPE-1 is mainly based on the reduction of the expression of disease markers, inhibition of apoptosis and stimulation of the autophagy process, which involves DNA methylation of specific genes.
• Selective modulation of the PPARγ receptor by amorfrutin B protects mouse neuronal cells from hypoxic-ischemic damage, which involves the mainteinance of mitochondrial integrity, inhibition of ROS synthesis and ROS-dependent DNA damage, as well as hypermethylation of the Pparg gene. Amorfrutin B also inhibits the activation of microglia.
• The aryl hydrocarbon receptor (AhR) may be a target for drugs to improve the pharmacotherapy of cerebral hypoxia. Inhibition of the AhR pathway is the primary mechanism of the protective effect of 3,3' diindolomethane (DIM) in neuronal cells exposed to hypoxia / ischemia, as well as in the rat brains subjected to perinatal asphyxia.
• Prenatal exposure to the pesticide DDT may be the cause of depressive disorders. This effect is specific to the p,p'-DDT isomer and is associated with a decrease in the levels of estrogen receptors ERα and GPR30 (now ESR1 and GPER1), hypermethylation of the relevant genes, and global DNA hypomethylation in the mouse brain.
Research methods
• Assessment of cell survival, cytotoxicity and oxidative stress markers, incl. staining with Calcein AM, AlamarBlue, NeuroFluor™ NeuO, measurement of lactate dehydrogenase (LDH) release and the use of 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA).
• Study of apoptosis and autophagy processes by measuring the levels of specific markers (including caspases, mitochondrial membrane potential, apoptotic bodies, autophagosomes).
• Molecular analyses, including gene expression measurement by qPCR and microarrays, protein expression measurement using ELISA and western blot methods, gene expression silencing using specific siRNAs.
• Epigenetic analyses, incl. measurement of DNA methylation, both global and specific genes, measurement of enzyme activity involved in histone modifications (HAT, HDAC, sirtuins), measurement of miRNA expression specific for central nervous system diseases.
• Immunofluorescence detection of specific proteins using confocal microscopy.
Keywords
Alzheimer’s disease, amorfrutin B, apoptosis, aryl hydrocarbon receptor (AhR), asphyxia, autophagy, bazedoxifene, 3,3'-diindolylmethane (DIM), daidzein, DDE, DDT, DNA methylation, epigenetics, estrogen receptors (ER / ESR; GPR30 / GPER1), excitotoxicity, genistein, hypoxia, in vitro models, iPSC, ischemia, microarrays, miRNA, molecular biology, neuroprotection, neurotoxicity, PaPE-1, 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
-
Amorfrutin B Protects Mouse Brain Neurons from Hypoxia/Ischemia by Inhibiting Apoptosis and Autophagy Processes Through Gene Methylation- and miRNA-Dependent Regulation.
Karolina Przepiórska, Agnieszka Wnuk, Cordian Beyer, Małgorzata Kajta
Molecular neurobiology, 10.1007/s12035-022-03087-9
PMID:36324052 -
Prenatal Exposure to Triclocarban Impairs ESR1 Signaling and Disrupts Epigenetic Status in Sex-Specific Ways as Well as Dysregulates the Expression of Neurogenesis- and Neurotransmitter-Related Genes in the Postnatal Mouse Brain.
Agnieszka Wnuk, Joanna Rzemieniec, Karolina Przepiórska, Bernadeta Angelika Pietrzak, Marzena Maćkowiak, Małgorzata Kajta
International journal of molecular sciences, 13121 10.3390/ijms222313121
PMID:34884933 -
Posttreatment Strategy Against Hypoxia and Ischemia Based on Selective Targeting of Nonnuclear Estrogen Receptors with PaPE-1.
A Wnuk, K Przepiórska, B A Pietrzak, M Kajta
Neurotoxicity research, 10.1007/s12640-021-00441-y
PMID:34797527 -
Is the commonly used UV filter benzophenone-3 a risk factor for the nervous system?
Agnieszka Wnuk, Małgorzata Kajta
Acta biochimica Polonica, 10.18388/abp.2020_5741
PMID:34351731 -
Post-Treatment with Amorfrutin B Evokes PPARγ-Mediated Neuroprotection against Hypoxia and Ischemia.
Agnieszka Wnuk, Karolina Przepiórska, Bernadeta A Pietrzak, Małgorzata Kajta
Biomedicines, 854 10.3390/biomedicines9080854
PMID:34440058 -
Selective Targeting of Non-nuclear Estrogen Receptors with PaPE-1 as a New Treatment Strategy for Alzheimer's Disease.
Agnieszka Wnuk, Karolina Przepiórska, Joanna Rzemieniec, Bernadeta Pietrzak, Małgorzata Kajta
Neurotoxicity research, 10.1007/s12640-020-00289-8
PMID:33025361 -
Neuroprotective effect of 3,3'-Diindolylmethane against perinatal asphyxia involves inhibition of the AhR and NMDA signaling and hypermethylation of specific genes.
J Rzemieniec, E Bratek, A Wnuk, K Przepiórska, E Salińska, M Kajta
Apoptosis : an international journal on programmed cell death, 10.1007/s10495-020-01631-3
PMID:32816128 -
Autophagy-related neurotoxicity is mediated via AHR and CAR in mouse neurons exposed to DDE.
Agnieszka Wnuk, Joanna Rzemieniec, Karolina Przepiórska, Julita Wesołowska, Anna Katarzyna Wójtowicz, Małgorzata Kajta
The Science of the total environment, S0048-9697(20)34121-8 10.1016/j.scitotenv.2020.140599
PMID:32721735 -
The neuroprotective action of 3,3'-diindolylmethane against ischemia involves an inhibition of apoptosis and autophagy that depends on HDAC and AhR/CYP1A1 but not ERα/CYP19A1 signaling.
J Rzemieniec, A Wnuk, W Lasoń, W Bilecki, M Kajta
Apoptosis : an international journal on programmed cell death, 10.1007/s10495-019-01522-2
PMID:30778709 -
Triclocarban impairs autophagy in neuronal cells and disrupts estrogen receptor signaling via hypermethylation of specific genes.
M Kajta, J Rzemieniec, A Wnuk, W Lasoń
The Science of the total environment, S0048-9697(19)34809-0 10.1016/j.scitotenv.2019.134818
PMID:31706213 -
Prenatal Exposure to Benzophenone-3 Impairs Autophagy, Disrupts RXRs/PPARγ Signaling, and Alters Epigenetic and Post-Translational Statuses in Brain Neurons.
Agnieszka Wnuk, Joanna Rzemieniec, Jakub Staroń, Ewa Litwa, Władysław Lasoń, Andrzej Bojarski, Małgorzata Kajta
Molecular neurobiology, 10.1007/s12035-018-1401-5
PMID:30402708 -
Triclocarban Disrupts the Epigenetic Status of Neuronal Cells and Induces AHR/CAR-Mediated Apoptosis.
M Kajta, A Wnuk, J Rzemieniec, W Lason, M Mackowiak, E Chwastek, M Staniszewska, I Nehring, A K Wojtowicz
Molecular neurobiology, 10.1007/s12035-018-1285-4
PMID:30097849 -
Effects of exposure to 5-MeO-DIPT during adolescence on brain neurotransmission and neurotoxicity in adult rats.
Karolina Noworyta-Sokołowska, Katarzyna Kamińska, Joanna Rzemieniec, Agnieszka Wnuk, Jakub Wojcieszak, Anna Maria Górska, Grzegorz Kreiner, Małgorzata Kajta, Krystyna Gołembiowska
Forensic toxicology, 10.1007/s11419-018-0433-x
PMID:30636982 -
The Effects of Exposure to Mephedrone During Adolescence on Brain Neurotransmission and Neurotoxicity in Adult Rats.
Katarzyna Kamińska, Karolina Noworyta-Sokołowska, Anna Górska, Joanna Rzemieniec, Agnieszka Wnuk, Adam Wojtas, Grzegorz Kreiner, Małgorzata Kajta, Krystyna Gołembiowska
Neurotoxicity research, 10.1007/s12640-018-9908-0
PMID:29713996 -
Prenatal exposure to benzophenone-3 (BP-3) induces apoptosis, disrupts estrogen receptor expression and alters the epigenetic status of mouse neurons.
Agnieszka Wnuk, Joanna Rzemieniec, Ewa Litwa, Władysław Lasoń, Małgorzata Kajta
The Journal of steroid biochemistry and molecular biology, S0960-0760(18)30103-1 10.1016/j.jsbmb.2018.04.016
PMID:29704544
- A popular-science article "From birth to old age - amorfrutin B in neuroprotection" Karolina Przepiórska
-
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.
-
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
Principal Investigator of the project: Bernadeta A. Pietrzak-Wawrzyńska, MSc,
The Scientific Supervisor of the project: Professor Małgorzata Kajta
-
Selective modulation of PPARγ signaling as a new therapeutic strategy for Alzheimer’s disease, Karolina Przepiórska-Drońska, PhD
NCN PRELUDIUM Grant; 2022/45/N/NZ7/01418; 2023-2026. Ongoing.
Principal Investigator of the grant: Karolina Przepiórska
The scientific supervisor of the grant: Professor Małgorzata Kajta
-
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
-
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
-
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, PhD
Thursday, 30 September 2021 -
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
Thursday, 22 November 2018 -
J. J. Supniewski Foundation award for scientific achievements., Professor Małgorzata Kajta, PhD
Wednesday, 25 February 2004
interests
techniques
keywords
- 3,3’-diindolylmethane
- ADHD
- Alzheimer disease
- animal models
- apoptosis
- aryl hydrocarbon receptor – AhR
- asphyxia
- autophagy
- Bazedoxifene
- Benzophenone-3
- confocal microscopy
- Daidzein
- DDE
- DDT
- depression
- DNA methylation
- epigenetics
- estrogen receptors
- estrogen receptors – ERs
- excitotoxicity
- fluorescent microscopy
- frontal cortex
- G-protein coupled receptors
- gene expression
- Genistein
- hippocampus
- hormones
- hypoxia
- hypoxia
- ischemia
- ischemia
- microarrays
- miRNA
- molecular biology
- necrosis
- neurodegeneration
- neurogenesis
- neuroprotection
- neurotoxicity
- peroxisome proliferator-activated receptors – PPARs
- pesticides
- pharmacotherapy
- phytoestrogens
- primary neuronal cell cultures
- Raloxifene
- retinoid X receptors – RXRs
- selective aryl hydrocarbon receptor modulators – SAhRMs
- selective estrogen receptor modulators – SERMs
- selective nuclear receptor modulators
- stem cells