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 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

Professor Małgorzata Kajta, dr hab.

Head

+48 12 6623235

kajta@if-pan.krakow.pl

room 52 A

Employees

Wojciech Krzeptowski, dr

+48 12 6623339

krzepto@if-pan.krakow.pl

room 128

Kinga Daniel, mgr inż.

daniel@if-pan.krakow.pl

Mikolaj Radosz, lic.

mikolaj.radosz@student.uj.edu.pl

Katarzyna Tomczyk

tomczyk@if-pan.krakow.pl

room 128