RNDr. Michal Dubovický, CSc
The foundations of the contemporary scientific team were formed in the early seventies of the 20th century when experimental teratology was incorporated into the Department of Toxicology, headed by Dr. Ladislav Vrbovský, CSc. Dr. Tatiana Balonová is considered to be a founder of reproductive and teratological studies at the Institute. The first experimental studies dealt with possible teratogenic and embryotoxic effects of the glycoprotein isolated from Candida albicans and its fractions, conducted in mice and rats. In cooperation with the Faculty of Natural Sciences, Comenius University in Bratislava, former Slovakofarma, n.p. Hlohovec and former Drug Research Institute, Modra more than 20 substances were tested for their teratogenicity (such as cyclophosphamide, etoffylline, exaprolol, pentacaine, bromadryl, stobadine and phenytoin). At the beginning of the 1990s one generation reproduction toxicity tests were extended to pre- and postnatal reproduction toxicity complemented by neurobehavioral development evaluation up to adulthood (neurobehavioral teratology). Moreover, behavioral toxicology screening tests in adult rats of both sexes have been introduced to current experimental practice. Independent Laboratory of Teratology headed by Dr. Eduard Ujházy was created in these years. In the period of millennium, the Laboratory was personnel expanded and within the reorganization of the Institute new Department of Reproductive Toxicology was established. Merging of the Institute with two other Institutes to Centre of Experimental Medicine of the Slovak Academy of Sciences in 2018 brought significant changes including connection of smaller units to Department of Molecular Pharmacology and Developmental Toxicology.
The scientific team deals with effects of chemical substances, including drugs, excessive stress and hypoxia/ischemia on developing organism. Other field of interest relates to psychopharmacological research of original substances designed at the Institute. Possible antidepressant activity of these substances is evaluated. Various experimental approaches are used to achieve scientific goals. Chronic mild unpredictable stress is used to induce depression-like state in experimental animas. Hypoxic chambers and/or ligation of carotids in neonatal rats are utilized to study effects of oxygen deficiency in developing organism focusing mainly on brain functioning. Rats and/or their offspring are subjected to complex behavioural screening including depression- and anxiety-like behaviour, exploratory activity and spatial memory. Hippocampal neurogenesis is investigated by means of specific immunohistochemical approaches, such as markers of proliferation (antibodies Ki67 and c-fos), cellular migration (doublecortin, reelin) and synaptogenesis (BDNF, synaptophysin). Levels of 5-HT, noradrenaline and dopamine in prefrontal cortex, striatum, hippocampus, hypothalamus and amygdala are measured by means of HPLC-ED method.
The scientific team intensively cooperates with other workplaces at the Slovak Academy of Sciences (Biomedical Research Centre, Centre of Biosciences) as well as with Universities (Faculty of Natural Sciences, Faculty of Medicine, Comenius University in Bratislava, Faculty of Chemical and Food Technology, Slovak Technical University in Bratislava).
Assoc. Prof. Eduard Ujházy and Dr. Michal Dubovický give lectures on teratology at the Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University in Bratislava. Members of the scientific team are involved in the toxicological studies in compliance with Good Laboratory Practice (acute oral and reproductive toxicity studies).
NAJVÝZNAMNEJŠIE PRÁCE ZA POSLEDNÉ OBDOBIE
Detection of sex-specific effects of excessive stress in neonatal period on exploratory behaviour, habituation and coping in new environment.
DUBOVICKÝ, Michal – TOKAREV, D. – ŠKULTÉTYOVÁ, Ivana – JEŽOVÁ, Daniela. Changes of exploratory behaviour and its habituation in rats neonatally treated with monosodium glutamate. In Pharmacology, biochemistry and behavior, 1997, vol. 56, no. 4, p. 565-569. (1.494 – IF1996). (1997 – Current Contents). ISSN 0091-3057.
DUBOVICKÝ, Michal – ŠKULTÉTYOVÁ, I. – JEŽOVÁ, Daniela. Neonatal stress alters habituation of exploratory behavior in adult male but not female rats. In Pharmacology, biochemistry and behavior, 1999, vol. 64, no. 4, p. 681-686. (1.612
IF1998). (1999 – Current Contents). ISSN 0091-3057.
Detection of delayed effect of short period of prenatal hypoxia on blood pressure and pulse in adult rats.
Sutovska, Hana – Molcan, Lubos – Koprdova, Romana – Piesova, Michaela – Mach, Mojmír – Zeman, Michal. Prenatal hypoxia increases blood pressure in male rat offspring and affects their response to artificial light at night. Journal of Developmental Origins of Health and Disease. Volume 12, Issue 4, Pages 587 – 594, August 2021
Detection of antidepressant-like properties of original substance SMe1EC2M3 via its triple 5-HT, norepinephrine, and dopamine reuptake inhibition.
Koprdova, Romana – Csatlosova, Kristina – Durisova, Barbora – Bogi, Eszter – Majekova, Magdalena – Dremencov, Eliyahu – Mach, Mojmir. Electrophysiology and behavioral assessment of the new molecule SMe1EC2M3 as a representative of the future class of triple reuptake inhibitors. Molecules Open Access. Volume 24, Issue 2320 November 2019 Article number 4218.
First teratology monography published in Slovakia.
Ujházy, Eduard – Michal, Dubovický – Mach, Mojmír. Teratológia: Princípy a mechanizmy abnormálneho vývinu. Slovenská toxikologická spoločnosť SETOX, 2014, 182, ISBN 9788096947461.
- ITN No. 813920 (HORIZON 2020): Molecular logic lab-on-a-vesicle for intracellular diagnostics (Mojmír Mach).
- MS26240220005 (SF EU): Transfer of knowledge and technologies from research and development in toxicology on evaluation of environmental and health risks (Michal Dubovický).
- APVV-15-0034: Investigation of anatomical-functional differences between the effects of aripiprazole and quetiapine, atypical antipsychotics with similar therapeutic indications, but different impact on brain dopaminergic receptors, in experimental animal (Alexander Kiss, Mojmír Mach).
- APVV-15-0388: Prenatal and postnatal effects opioid receptor ligands on the hippocampal development and function (Ľubica Lacinová, Michal Dubovický).
- APVV-19-0435: Novel antidepressant therapy – long teram effects on offspring (Ľubica Lacinová, Michal Dubovický).
- VEGA 2/0166/16: Prenatal programming of psychiatric diseases: experimental approaches for evaluation of causes and mechanisms of their origin (Mojmír Mach).
- VEGA 2/0124/19: Experimental study of effect of maternal depression and antidepressant treatment during pregnancy and lactation on health of the mother and developing offspring (Michal Dubovický).
- VEGA 2/0154/20: Prenatal programming of adult diseases and possibilities to treat and prevent consequences of prenatal hypoxia in rat offspring (Mojmír Mach).
- VEGA 2/0154/20: Experimental treatment of neonatal hypoxic-ischemic encephalopathy by potentiation of hypothermic neuroprotection with melatonin in neonatal rats (Ivo Juránek).
The scientific team plans broaden experimental models of depressive disorder focusing mainly on resistant form of depression and ways of its treatment. Moreover, focus will be also on selected gene expressions in placenta and brain in stressed and antidepressant treated animals to find possible pathophysiological mechanisms which finally lead to an injury and/or disorder/disease. Further domestic and international cooperation will be promoted and supported (such as Faculty of Natural Sciences, Charles University, Czech Republic).