Publications by authors named "Kamilla Blecharz-Klin"

26 Publications

  • Page 1 of 1

Early exposure to paracetamol reduces level of testicular testosterone and changes gonadal expression of genes relevant for steroidogenesis in rats offspring.

Drug Chem Toxicol 2021 Mar 3:1-8. Epub 2021 Mar 3.

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Warsaw, Poland.

In this study, we investigated the effects of early paracetamol treatment on the testicular level of testosterone and expression of genes important for steroid biosynthesis and reproduction in male rats offspring. Rats were continuously exposed to paracetamol at doses of 5 or 15 mg/kg b.w. during pregnancy and the first two months of the postpartum development. Testosterone level was determined by ELISA. Profile of gene expression for the testicular steroidogenic factors were evaluated using the Real-Time PCR. Our results showed that paracetamol reduces testicular testosterone level and causes compensatory transactivation of genes important for steroidogenesis and reproductive capacity. We have observed significant over-expression of several genes involved in cholesterol transport and steroid biosynthesis e.g., genes for steroidogenic acute regulatory protein, hydroxysteroid dehydrogenases, luteinizing hormone subunit beta, gonadotropin and androgen receptors. Up-regulation of these genes with parallel testosterone reduction in the testicles could be the possible mechanism that maintains and prevents the loss of the steroidogenic function.
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http://dx.doi.org/10.1080/01480545.2021.1892941DOI Listing
March 2021

Aspalathus linearis infusion affects hole-board test behaviour and amino acid concentration in the brain.

Neurosci Lett 2021 03 30;747:135680. Epub 2021 Jan 30.

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Banacha 1b, 02-097, Warsaw, Poland.

Rooibos tea, brewed using Aspalathus linearis leaves, is a popular South African herbal infusion, but its everyday intake is not fully described in terms of the neuropsychopharmacological outcomes. The cell-protective activity of A. linearis is connected with the ability of reducing glycaemia, inflammation as well as oxidative stress. It was already shown that "fermented" rooibos herbal tea (FRHT), which is rich in phenolic compounds, improves the cognitive performance of rats in the water maze and impacts dopaminergic striatal transmission. The present research was taken to extend the knowledge about the feasible behavioural and neurochemical implications of sustained oral FRHT consumption. We hypothesized that it might affect brain amino acid content and thus induce behaviour and neuroprotection. FRHTs of different leaf to water ratios (1:100, 2:100 and 4:100), analysed by chromatographic methods as regards their flavonoid characteristics, were given to rats as only liquid for 3 months. Their behaviour was evaluated in the hole-board test (HBT). Brain amino acids concentration was analysed in the striatum, hippocampus and prefrontal cortex by HPLC-ECD. The rats drinking rooibos tea presented increased motor activity defined as time spent on moving in the HBT. Their exploration measured by head-dipping and rearing was enhanced. Longer time of the testing-box central zone occupation indicated to reduction in anxiety-related behaviour. Excitatory amino acids (aspartate and glutamate) content was decreased in the striatum of animals drinking the infusions whereas taurine level was increased both in the striatum and hippocampus. In conclusion we suggest that long-term FRHT intake affects exploration and anxiety-related behaviour of the rats as well as exerts biochemical outcomes in the brain that support the neuroprotective impact of rooibos tea.
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http://dx.doi.org/10.1016/j.neulet.2021.135680DOI Listing
March 2021

Effect of protocatechuic acid on cognitive processes and central nervous system neuromodulators in the hippocampus, prefrontal cortex, and striatum of healthy rats.

Nutr Neurosci 2020 Dec 21:1-12. Epub 2020 Dec 21.

Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology CePT, Medical University of Warsaw, Warsaw, Poland.

Objective: : This study aimed to investigate the influence of protocatechuic acid (PCA) on learning, memory, and central nervous system (CNS) neuromodulators in healthy rats, to analyse whether the procognitive effects of PCA found in animal models of memory impairment and described in the literature occur in healthy individuals.

Methods: : PCA was administered for 48 days at doses of 50 or 100 mg/kg body weight. The cognitive performance was analysed in behavioural tests (open field, novel object recognition, water maze). Then the animals were sacrificed and their hippocampi, prefrontal cortices and striata removed to measure the level of serotonin, dopamine (DA), noradrenaline, their metabolites and amino acids (taurine, histidine, serine, glutamic acid, aspartic acid, γ-aminobutyric acid, alanine) using high-performance liquid chromatography.

Results: : No obvious behavioural changes were observed. Post-mortem quantification of monoamines showed that the turnover of DA in the striatum was significantly increased by PCA. Moreover, hippocampal, and cortical levels of histidine were influenced by PCA and significantly decreased.

Conclusion: : Despite many beneficial effects of PCA in experimentally developed cognitive impairments, it has no sharp effect on memory performance in healthy rats. The influence on the turnover of striatal DA and modulation of the amino acid system by affecting the concentration of histidine deserves a deeper examination due to the role of histamine in neuropsychiatric disorders as well as the functional interactions between histidine and DA metabolism in the brain.
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http://dx.doi.org/10.1080/1028415X.2020.1859728DOI Listing
December 2020

Hypothalamus - Response to early paracetamol exposure in male rats offspring.

Int J Dev Neurosci 2019 Aug 21;76:1-5. Epub 2019 May 21.

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Banacha 1B, 02-097, Warsaw, Poland.

One of the reasons for using paracetamol during pregnancy is fever. The brain structure responsible for maintaining proper body temperature, but also for controlling some endocrine aspects is hypothalamus. In this study we examined the effect of early pretreatment of paracetamol on hypothalamic neurotransmission in rats' offspring. We used two-month old rats previously exposed to paracetamol at doses of 5 (P5) and 15 mg/kg (P15) during gestational development and next postnatally. The concentration of monoamines, their metabolites and amino acids in hypothalamus was chromatographically determined. The results of biochemical analysis were compared with the Control animals (Con). We found differences between groups in the concentration of main noradrenaline metabolite in hypothalamus. The control group had significantly higher level of 3-methoxy-4-hydroxyphenylglycol (MHPG) compared with rats exposed to paracetamol (F = 7.96, p < 0.005). Simultaneously the level of dopamine (DA) (F = 4.33, p < 0.05) and its metabolite - homovanillic acid (HVA) (F = 17.03, p < 0.005) was increased in the hypothalamus of animals treated with lower dose of the drug. Biochemical analyses show an increase in 3,4-dihydroxyphenyl acetic acid (DOPAC) concentration in P5 group compared to the control rats and group treated with higher dose of paracetamol (F = 7.37, p < 0.005). In the hypothalamus significant decrease of glutamic acid concentration was also observed in the group treated with paracetamol at dose of 5 mg. These results demonstrated that paracetamol had a significant effect on dopaminergic and noradrenergic neurotransmission and changed the concentration of glutamic acid in hypothalamus - heat-regulating center and important element of hypothalamic-pituitary- gonadal axis.
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http://dx.doi.org/10.1016/j.ijdevneu.2019.05.004DOI Listing
August 2019

Long-term administration of Aspalathus linearis infusion affects spatial memory of adult Sprague-Dawley male rats as well as increases their striatal dopamine content.

J Ethnopharmacol 2019 Jun 16;238:111881. Epub 2019 Apr 16.

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Banacha 1b, 02-097, Warsaw, Poland. Electronic address:

Ethnopharmacological Relevance: Everyday use of the herbal tea rooibos, produced from Aspalathus linearis (Brum.f) Dahlg. (Fabaceae) is customary in South Africa, a continuation of its historical use by indigenous people. Although evidence of its traditional indications is anecdotal, rooibos tea is regarded as a general health tea.

Aims Of The Study: Available contemporary research indicates to broad cell protective activity of rooibos focusing on its antioxidative, anti-inflammatory, anti-hyperglycaemic and antithrombotic features affecting metabolic syndrome, cardiovascular risk and neuroprotection. Nevertheless little is known about its impact on brain functions. The present experiment aimed to evaluate the possible behavioural and neurochemical effects of long-term oral administration of "fermented" rooibos herbal tea (FRHT) infusions to adult male Sprague-Dawley rats.

Materials And Methods: Infusions, prepared using 1, 2 and 4 g of "fermented" (oxidised) A. linearis leaves for 100 ml of hot water, were characterised in terms of flavonoid content by ultra-high and high performance liquid chromatography (UHPLC-qTOF-MS, HPLC-DAD) and administered to rats as sole drinking fluid for 12 weeks. Spatial memory behaviour was assessed in a modified version of the Morris water maze. Dopamine, noradrenaline, serotonin and their metabolite levels (DOPAC, 3-MT, HVA, MHPG, 5-HIAA) were quantified in prefrontal cortex, hippocampus and striatum by HPLC-ECD. Body weight and blood glucose level were additionally estimated.

Results: All FRHT-treated rats showed improvement of long-term spatial memory defined as increased number of crossings over the previous platform position in SE quadrant of the water maze. It was not accompanied by excessive motor activity. Striatal dopamine and its metabolite 3-MT (3-methoxytyramine) levels were increased in treated rats. There were no differences in body weight gain between control and treated animals but blood glucose level was significantly lower in the latter ones.

Conclusion: The improvement of long-term memory in FRHT-treated rats and stimulating impact of FRHT on their dopaminergic striatal transmission support the wellness enhancing effect of rooibos tea, contributing to a better understanding of the neurological background of traditional habitual consumption of this herbal tea.
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http://dx.doi.org/10.1016/j.jep.2019.111881DOI Listing
June 2019

Administration of protocatechuic acid affects memory and restores hippocampal and cortical serotonin turnover in rat model of oral D-galactose-induced memory impairment.

Behav Brain Res 2019 08 9;368:111896. Epub 2019 Apr 9.

Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology CePT, Medical University of Warsaw, Banacha 1b, 02-097 Warsaw, Poland. Electronic address:

Protocatechuic acid (PCA) is a phenolic compound believed to have neuroprotective and procognitive activity. d-Galactose (D-Gal) is a sugar, which administered to mammals can induce cognitive deficits. The first aim of this study was to confirm the effectiveness of D-Gal administered orally in inducing cognitive impairment in rats and describe how it affects the concentration of neurotransmitters in rats' brain. The second aim was to evaluate the influence of PCA on learning, memory and neurotransmission in D-Gal-exposed rats. Memory impairment was induced by long-term administration of D-Gal (100 mg/kg body weight/day) directly via oral gavage. PCA (50 or 100 mg/kg body weight/day, respectively) was administered in drinking water. Morris Water Maze test (MWM) to assess learning and spatial memory was initiated after 38 days of treatment and lasted for 10 days. The concentrations of monoamines and their metabolites were evaluated in selected brain regions using high performance liquid chromatography. D-Gal significantly impaired cognitive performance during the acquisition and recall of MWM compared to control rats and changed concentrations of cortical serotonin as well as its cortical and hippocampal turnover. The turnover of dopamine was also influenced by D-Gal. Simultaneously, PCA was found to improve retrieval of acquired information in MWM and to restore brain serotonergic and dopaminergic turnover dysregulated by D-Gal. These findings confirm the usefulness of oral D-Gal in eliciting rat model of mild memory impairment and show that long-term administration of PCA can be beneficial in reversing detrimental changes related to cognitive deficiencies.
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http://dx.doi.org/10.1016/j.bbr.2019.04.010DOI Listing
August 2019

Long-term administration of Greek Royal Jelly decreases GABA concentration in the striatum and hypothalamus of naturally aged Wistar male rats.

Neurosci Lett 2018 05 22;675:17-22. Epub 2018 Mar 22.

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Banacha 1B, 02-097, Warsaw, Poland.

Royal Jelly (RJ) is a unique substance obtained from bees that has been used widely in European and Asian traditional medicine for its potential to prevent signs of aging through its antioxidative, anti-inflammatory, anti-hyperglycemic and anti-hypercholesterolemic properties. We recently reported an enhancement in spatial memory along with changes in monoaminergic transmission in aged rats after chronic RJ administration. Here, we aim to further explore the action of RJ on central nervous system activity by examining levels of amino acids in selected brain structures of aged male Wistar rats following 2-months of Greek RJ administration. RJ powder was previously chemically characterized and given orally (50 or 100 mg of powder/kg b.w./day) by gastric gavage. The concentrations of amino acids (alanine, aspartic acid, gamma-aminobutyric acid, glutamic acid, histidine and taurine) in the brain regions examined (prefrontal cortex, hippocampus, striatum and hypothalamus) were quantified using HPLC. We also examined basic biochemical parameters of renal and hepatic activity, as damage of these organs could potentially explain the changes in brain function and behavior. Upon biochemical examination, a decrease in the concentration of gamma-aminobutyric acid was observed in both the striatum and hypothalamus. Liver and kidney functions were not changed by chronic RJ-administration. Our results provide insight toward understanding the mechanism of action of RJ and its effects on neurotransmission in the central nervous system.
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http://dx.doi.org/10.1016/j.neulet.2018.03.034DOI Listing
May 2018

Early paracetamol exposure decreases brain-derived neurotrophic factor (BDNF) in striatum and affects social behaviour and exploration in rats.

Pharmacol Biochem Behav 2018 05 13;168:25-32. Epub 2018 Mar 13.

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Banacha 1B, 02-097 Warsaw, Poland.

The biochemical and behavioral responses to prenatal and early postnatal exposure to paracetamol in rats are not well understood. The effect of daily maternal and early life administration of 5 mg/kg (group P5) or 15 mg/kg paracetamol (group P15) was evaluated in two-month old male rats, relative to control animals receiving tap water (Con). Social behavior and episodic memory were investigated with Social Interaction and Novel Object Recognition (NOR) tests. Quantification of brain-derived neurotrophic factor (BDNF) was determined in prefrontal cortex, hippocampus and striatum using enzyme-linked immunosorbent assay (ELISA). Control animals exhibited a higher total frequency of social interactions and greater frequency of sniffing compared to rats exposed to paracetamol, and we found a statistically significant increase in the occurrence of pinning in paracetamol-treated animals. Rats from the 15 mg/kg group exhibited a greater interest in objects in the NOR test and spent more time exploring objects during the familiarization and choice phases. Biochemical analysis showed significant differences in striatal BDNF between the groups, specifically, a nearly two-fold decrease in striatal BDNF in the paracetamol groups (P5: 6.78 ± 0.60 pg/mg; P15: 6.06 ± 0.46 pg/mg) relative to the control group (Con: 11.33 ± 2.00 pg/mg). These results indicate that paracetamol exposure induces changes in social behaviour and exploration in rats and results in a significant decrease of striatal BDNF.
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http://dx.doi.org/10.1016/j.pbb.2018.03.004DOI Listing
May 2018

Paracetamol - Effect of early exposure on neurotransmission, spatial memory and motor performance in rats.

Behav Brain Res 2017 04 3;323:162-171. Epub 2017 Feb 3.

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Banacha 1B, 02-097 Warsaw, Poland. Electronic address:

In the present study we examined the effect of prenatal and early life paracetamol exposure on neurotransmission and its behavioural manifestation in rat male pups. In order to assess the ability of spatial learning and memory consolidation and the level of physical and exploratory activity we conducted a series of behavioural tests: Staircase Test, Hole Board Test and Water Maze. The concentrations of monoamines, metabolites and amino acids were determined using High Performance Liquid Chromatography in the prefrontal cortex, hippocampus and striatum. The effect on spatial memory and exploratory behaviour was most pronounced in animals treated with the lower dose of paracetamol. In this group we have observed a much lower motor activity and decreased head-dipping behaviour. Simultaneously, the number of crossings in the Water Maze under the previous platform position during the probe trial was significantly higher in rats treated with paracetamol at the dose of 5mg/kg. There was also a preference for a new location of a platform to the original position of the platform in the reversal probe trial of this group. These results indicate that early paracetamol exposure produces major changes in serotonergic and dopaminergic neurotransmission in the prefrontal cortex and striatum. At the same time, administration of the drug in early life results in the spectacular change in the amino acid level, in particular in the hippocampus and cortex. This has been reflected in the behaviour of animals in the Water Maze and Hole Board Test (without any noticeable impact on the Staircase Test).
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http://dx.doi.org/10.1016/j.bbr.2017.01.051DOI Listing
April 2017

Cerebellar level of neurotransmitters in rats exposed to paracetamol during development.

Pharmacol Rep 2016 Dec 7;68(6):1159-1164. Epub 2016 Sep 7.

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Warszawa, Poland. Electronic address:

Background: The present study was designed to clarify the effect of prenatal and postnatal paracetamol administration on the neurotransmitter level and balance of amino acids in the cerebellum.

Methods: Biochemical analysis to determine the concentration of neurotransmitters in this brain structure was performed on two-month-old Wistar male rats previously exposed to paracetamol in doses of 5 (P5, n=10) or 15mg/kg (P15, n=10) throughout the entire prenatal period, lactation and until the completion of the second month of life, when the experiment was terminated. Control animals were given tapped water (Con, n=10). The cerebellar concentration of monoamines, their metabolites and amino acids were assayed using High Performance Liquid Chromatography (HPLC).

Results: The present experiment demonstrates that prenatal and postnatal paracetamol exposure results in modulation of cerebellar neurotransmission with changes concerning mainly 5-HIAA and MHPG levels.

Conclusion: The effect of paracetamol on monoaminergic neurotransmission in the cerebellum is reflected by changes in the level of catabolic end-products of serotonin (5-HIAA) and noradrenaline (MHPG) degradation. Further work is required to define the mechanism of action and impact of prenatal and postnatal exposure to paracetamol in the cerebellum and other structures of the central nervous system (CNS).
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http://dx.doi.org/10.1016/j.pharep.2016.06.005DOI Listing
December 2016

Passiflora incarnata L. Improves Spatial Memory, Reduces Stress, and Affects Neurotransmission in Rats.

Phytother Res 2016 May 27;30(5):781-9. Epub 2016 Jan 27.

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Banacha 1B, 02-097, Warsaw, Poland.

Passiflora incarnata L. has been used as a medicinal plant in South America and Europe since the 16th century. Previous pharmacological studies focused mainly on the plant's sedative, anxiolytic, and anticonvulsant effects on the central nervous system and its supporting role in the treatment of addiction. The aim of the present study was to evaluate the behavioral and neurochemical effects of long-term oral administration of P. incarnata. The passionflower extract (30, 100, or 300 mg/kg body weight/day) was given to 4-week-old male Wistar rats via their drinking water. Tests were conducted after 7 weeks of treatment. Spatial memory was assessed in a water maze, and the levels of amino acids, monoamines, and their metabolites were evaluated in select brain regions by high performance liquid chromatography (HPLC). We observed reduced anxiety and dose-dependent improvement of memory in rats given passionflower compared to the control group. In addition, hippocampal glutamic acid and cortical serotonin content were depleted, with increased levels of metabolites and increased turnover. Thus, our results partially confirmed the proposed mechanism of action of P. incarnata involving GABAA receptors. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/ptr.5578DOI Listing
May 2016

Influence of Long-Term Zinc Administration on Spatial Learning and Exploratory Activity in Rats.

Biol Trace Elem Res 2016 Aug 6;172(2):408-418. Epub 2016 Jan 6.

Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology CePT, Medical University of Warsaw, Banacha 1b, 02-097, Warsaw, Poland.

Animal brain contains a significant amount of zinc, which is a cofactor for more than 300 enzymes. Moreover, it provides the basis for functioning of more than 2000 transcription factors, and it is necessary for memory formation and learning processes in the brain. The aim of this study was to investigate the effect of zinc supplementation on behavior in 3-month-old rats. For this purpose, the Morris water maze paradigm, hole-board, and T-maze were used. Wistar rats received a solution of ZnSO4 in drinking water at the doses of 16 mg/kg (Zn16 group) and 32 mg/kg (Zn32 group). In rats pretreated with the lower dose of zinc, the improvement of the mean escape latency was observed in comparison to the control group and Zn32 group. During memory task, both ZnSO4-supplemented groups showed an increase in crossings over the previous platform position. Furthermore, the exploratory activity in Zn16 group was improved in comparison to Zn32 and control group. In the brains of zinc-supplemented rats, we observed the higher content of zinc, both in the hippocampus and the prefrontal cortex. Hippocampal zinc level correlated positively with the mean annulus crossings of the Zn16 group during the probe trial. These findings show that the long-term administration of ZnS04 can improve learning, spatial memory, and exploratory activity in rats. Graphical Abstract Improvement of spatial learning, memory, and exploratory behavior.
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http://dx.doi.org/10.1007/s12011-015-0597-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930948PMC
August 2016

Effect of prenatal and early life paracetamol exposure on the level of neurotransmitters in rats--Focus on the spinal cord.

Int J Dev Neurosci 2015 Dec 25;47(Pt B):133-9. Epub 2015 Sep 25.

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Banacha 1B, 02-097 Warsaw, Poland. Electronic address:

The present study has examined the influence of the prenatal and early life administration of paracetamol on the level of neurotransmitters in the spinal cord of rat pups. The effect of the drug was evaluated in 2-month old Wistar male rats exposed to paracetamol in doses of 5 (P5, n=9) or 15 mg/kg (P15, n=9) p.o. during the prenatal period and after birth until the completion of the second month of life. A parallel control group received tap water (Con, n=9). In this study we have determined the level of monoamines, their metabolites and amino acids in the spinal cord of rats using high performance liquid chromatography (HPLC) in the second month of life. The present experiment demonstrates the action of paracetamol at the molecular level associated with significant modulation of neurotransmission in the spinal cord related to dopaminergic and noradrenergic systems. Simultaneously, paracetamol administration increases the content of an aspartic and glutamic acids in the spinal cord at a critical time during development.
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http://dx.doi.org/10.1016/j.ijdevneu.2015.09.002DOI Listing
December 2015

Developmental exposure to paracetamol causes biochemical alterations in medulla oblongata.

Environ Toxicol Pharmacol 2015 Sep 4;40(2):369-74. Epub 2015 Jul 4.

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology CePT, Banacha 1B, 02-097 Warsaw, Poland. Electronic address:

The effect and safety of prenatal and early life administration of paracetamol - routinely used over-the-counter antipyretic and analgesic medication on monoamines content and balance of amino acids in the medulla oblongata is still unknown. In this study we have determined the level of neurotransmitters in this structure in two-month old Wistar male rats exposed to paracetamol in the dose of 5 (P5, n=10) or 15mg/kg b.w. (P15, n=10) during prenatal period, lactation and till the end of the second month of life. Control group received drinking water (Con, n=10). Monoamines, their metabolites and amino acids concentration in medulla oblongata of rats were determined using high performance liquid chromatography (HPLC) in 60 postnatal day (PND60). This experiment shows that prenatal and early life paracetamol exposure modulates neurotransmission associated with serotonergic, noradrenergic and dopaminergic system in medulla oblongata. Reduction of alanine and taurine levels has also been established.
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http://dx.doi.org/10.1016/j.etap.2015.07.001DOI Listing
September 2015

Long-term administration of Greek Royal Jelly improves spatial memory and influences the concentration of brain neurotransmitters in naturally aged Wistar male rats.

J Ethnopharmacol 2014 Aug 29;155(1):343-51. Epub 2014 May 29.

Department of Experimental and Clinical Pharmacology, Medical University, of Warsaw, Banacha 1b, 02-097 Warsaw, Poland. Electronic address:

Ethnopharmacological Relevance: Royal Jelly (RJ) is a bee-derived product that has been traditionally used in the European and Asian systems of medicine for longevity. RJ has various pharmacological activities that may prevent aging e.g., anti-inflammatory, anti-oxidative, anti-hypercholesterolemic and anti-hyperglycemic properties.

Aim Of The Study: To evaluate the behavioral and neurochemical effects of long-term oral, previously chemically analyzed, Greek RJ administration to aged rats.

Materials And Methods: RJ powder was given to 18-month old male Wistar rats (50 and 100mg of powder/kg b.w./day) by gastric gavage for 2 months. The spatial memory was assessed in the water maze and next the level of neurotransmitters, their metabolites and utilization in the selected brain regions were estimated.

Results: The improvement of memory in rats pretreated with the smaller dose of RJ was observed compared with controls. In biochemical examination mainly the depletion of dopamine and serotonin in the prefrontal cortex along with an increase in their metabolite concentration and turnover were seen.

Conclusion: Better cognitive performance in the old animals using a non-toxic, natural food product in the view of the process of the aging of human population is noteworthy. Our results contribute towards validation of the traditional use of RJ in promoting a better quality of life in old age.
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http://dx.doi.org/10.1016/j.jep.2014.05.032DOI Listing
August 2014

Paracetamol impairs the profile of amino acids in the rat brain.

Environ Toxicol Pharmacol 2014 Jan 13;37(1):95-102. Epub 2013 Nov 13.

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Krakowskie Przedmieście 26/28, 00-927 Warsaw, Poland. Electronic address:

In our experiment we investigated the effect of subcutaneous administration of paracetamol on the levels of amino acids in the brain structures. Male Wistar rats received for eight weeks paracetamol at two doses: 10 mg/kg b.w. (group P10, n=9) and 50 mg/kg b.w. per day s.c. (group P50, n=9). The regional brain concentrations of amino acids were determined in the prefrontal cortex, hippocampus, hypothalamus and striatum of control (Con, n=9) and paracetamol-treated groups using HPLC. Evaluation of the biochemical results indicated considerable decrease of the content of amino acids in the striatum (glutamine, glutamic acid, taurine, alanine, aspartic acid) and hypothalamus (glycine) between groups treated with paracetamol compared to the control. In the prefrontal cortex paracetamol increased the level of γ-aminobutyric acid (GABA). The present study demonstrated significant effect of the long term paracetamol treatment on the level of amino acids in the striatum, prefrontal cortex and hypothalamus of rats.
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http://dx.doi.org/10.1016/j.etap.2013.11.004DOI Listing
January 2014

Paracetamol--the outcome on neurotransmission and spatial learning in rats.

Behav Brain Res 2013 Sep 11;253:157-64. Epub 2013 Jul 11.

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Krakowskie Przedmieście 26/28, 00-927 Warsaw, Poland.

The present study was aimed at investigating the effect of subcutaneous (s.c.) paracetamol administration on spatial learning, memory and neurotransmission. Three-month old male Wistar rats received for eight weeks paracetamol at two doses: 10mg/kg b.w. (group P10, n=9) or 50mg/kg b.w. per day s.c. (group P50, n=9). Control (Con, n=9) and paracetamol-treated groups have been observed for behavioral performance and learning in the modified Morris water maze task. After completion of the behavioral data, the regional brain concentrations of neurotransmitters and their metabolites were determined using High Performance Liquid Chromatography (HPLC) in the prefrontal cortex, hippocampus, hypothalamus and the striatum. ANOVA for repeated measurements did not show significant differences between the groups in the acquisition in the water maze test. However, working memory improvement was noticed in P10 and P50 during second day of training. Results of the probe trial on day 6 indicated an increase in the mean swimming speed following subcutaneous drug treatment. Significant differences in the content of monoamines and metabolites between the experimental groups suggests that major changes after paracetamol administration are related to serotonergic and noradrenaline neurotransmission in the prefrontal cortex, hypothalamus and the striatum. The present experiment demonstrates that eight-week long subcutaneous paracetamol treatment results in significant modulation of neurotransmission with subtle changes concerning behavior and working memory in rats.
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http://dx.doi.org/10.1016/j.bbr.2013.07.008DOI Listing
September 2013

Influence of long-term administration of rutin on spatial memory as well as the concentration of brain neurotransmitters in aged rats.

Pharmacol Rep 2012 ;64(4):808-16

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warszawa, Poland.

Background: The present study was designed to investigate the behavioral and neurochemical effects of long-term oral rutin administration to old male WAG rats (100 and 200 mg/kg b.w./day). Rutin is a well-known dietary flavonol glycoside with antioxidant and anti-inflammatory properties.

Methods: First, spatial memory was assessed in the water maze and then the levels of neurotransmitters in selected brain regions were estimated.

Results: There was enhanced spatial memory in aged rats pretreated with the smaller dose of rutin in the probe trial of the water maze, nevertheless, augmented levels of noradrenaline in the hippocampi of these animals were not correlated with improved spatial memory. The increased dopamine levels in the hypothalami of the same group of animals may suggest effects other than behavioral.

Conclusion: Long-term rutin pre-treatment may cause behavioral and neurochemical changes in aged WAG male rats.
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http://dx.doi.org/10.1016/s1734-1140(12)70876-9DOI Listing
June 2013

Effect of intranasal manganese administration on neurotransmission and spatial learning in rats.

Toxicol Appl Pharmacol 2012 Nov 27;265(1):1-9. Epub 2012 Sep 27.

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Krakowskie Przedmieście 26/28, 00-927 Warsaw, Poland.

The effect of intranasal manganese chloride (MnCl(2)·4H(2)O) exposure on spatial learning, memory and motor activity was estimated in Morris water maze task in adult rats. Three-month-old male Wistar rats received for 2weeks MnCl(2)·4H(2)O at two doses the following: 0.2mg/kg b.w. (Mn0.2) or 0.8mg/kg b.w. (Mn0.8) per day. Control (Con) and manganese-exposed groups were observed for behavioral performance and learning in water maze. ANOVA for repeated measurements did not show any significant differences in acquisition in the water maze between the groups. However, the results of the probe trial on day 5, exhibited spatial memory deficits following manganese treatment. After completion of the behavioral experiment, the regional brain concentrations of neurotransmitters and their metabolites were determined via HPLC in selected brain regions, i.e. prefrontal cortex, hippocampus and striatum. ANOVA demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the controls. Negative correlations between platform crossings on the previous platform position in Southeast (SE) quadrant during the probe trial and neurotransmitter turnover suggest that impairment of spatial memory and cognitive performance after manganese (Mn) treatment is associated with modulation of the serotonergic, noradrenergic and dopaminergic neurotransmission in the brain. These findings show that intranasally applied Mn can impair spatial memory with significant changes in the tissue level and metabolism of monoamines in several brain regions.
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http://dx.doi.org/10.1016/j.taap.2012.09.015DOI Listing
November 2012

Neonatal serotonin (5-HT) depletion does not affect spatial learning and memory in rats.

Pharmacol Rep 2012 ;64(2):266-74

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Krakowskie Przedmieście 26/28, PL 00-927 Warszawa, Poland.

Background: Extensive previous research has suggested a role for serotonin (5-HT) in learning and memory processes, both in healthy individuals and pathological disorders including depression, autism and schizophrenia, most of which have a developmental onset. Since 5-HT dysfunction in brain development may be involved in disease etiology, the present investigation assessed the effects of neonatal 5-HT depletion on spatial learning and memory in the Morris water maze (MWM).

Methods: Three days old Sprague-Dawley rats were pretreated with desipramine (20 mg/kg) followed by an intraventricular injection of the selective 5-HT neurotoxin 5,7-dihydroxytryptamine (5,7-DHT, 70 μg). Three months later rats were tested in the MWM.

Results: Despite a severe and permanent decrease (80-98%) in hippocampal, prefrontal and striatal 5-HT levels, treatment with 5,7-DHT caused no spatial learning and memory impairment.

Conclusions: Limited involvement of chronic 5-HT depletion on learning and memory does not exclude the possibility that this neurotransmitter has an important neuromodulatory role in these functions. Future studies will be needed to identify the nature of the compensatory processes that are able to allow normal proficiency of spatial learning and memory in 5-HT-depleted rats.
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http://dx.doi.org/10.1016/s1734-1140(12)70764-8DOI Listing
November 2012

Maternal zinc supplementation improves spatial memory in rat pups.

Biol Trace Elem Res 2012 Jun 17;147(1-3):299-308. Epub 2012 Jan 17.

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland.

A large body of evidence supports an opinion that adequate dietary zinc is essential for prenatal and postnatal brain development. Behavioural effects of maternal supplementation with ZnSO(4) were analysed in rat pups with the Morris water task performance, a hole board and a T-maze. Wistar females during pregnancy and lactation received a drinking water solution of ZnSO(4) at doses of 16 mg/kg (group Zn16) or 32 mg/kg (group Zn32). Behavioural tests were conducted on the 4-week-old male rat pups. Zinc concentration in the serum, hippocampus and prefrontal cortex of offsprings was determined by means of atomic absorption techniques. The Newman-Keuls multiple comparison test revealed an increase of climbing in the Zn16 group in comparison to the control group (Con) and the Zn32 group during the hole board test. ANOVA for repeated measures showed a significant memory improvement in both supplemented groups compared to the control in the probe trial on day 5 of the water maze test. ZnSO(4) treatment significantly elevated zinc levels in the rat serum. Follow-up data on brain content of zinc in the hippocampus revealed significant differences between the groups and in supplemented groups correlated with crossings above the original platform position. These findings suggest that pre- and postnatal zinc supplementation may improve cognitive development in rats.
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http://dx.doi.org/10.1007/s12011-012-9323-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362702PMC
June 2012

The influence of the long-term administration of Curcuma longa extract on learning and spatial memory as well as the concentration of brain neurotransmitters and level of plasma corticosterone in aged rats.

Pharmacol Biochem Behav 2010 May 26;95(3):351-8. Epub 2010 Feb 26.

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Krakowskie Przedmieście 26/28, 00-927 Warsaw, Poland.

The effects of chronic pre-treatment with a standardised extract of Curcuma longa on learning and spatial memory in aged 24-month old male Wistar rats were estimated in a Morris water maze paradigm. Animals received the extract orally for two months in prepared rodent chow to obtain the doses 10 and 50mg/kg/day. At the end of behavioural trials the concentration of neurotransmitters, their metabolites and amino acids in selected brain regions were estimated. There was a significant decrease in escape latency over four days of training in both treated groups in comparison to the control group. In a probe trial on the 5th day the C10 group crossed the target area more often and spent more time in the SE quadrant than control group. Significant differences in brain monoamines and amino acid levels between groups were noticed. The increase in the 5-HT (5-hydroxytryptamine) level in the prefrontal cortex correlated positively with the number of crossings over the target area during the first probe trial in both pre-treated groups. The plasma corticosterone level was lower in both pre-treated groups than in the control group. This suggests enhanced learning ability and spatial memory after C.longa extract treatment with the modulation of central serotoninergic system activity, and may be linked with an increased tolerance to stress conditions. A decrease in hippocampal glutamate in animals given plant extract compared to control rats was observed. It is possible that extract may influence a reduction in glutamate-induced excitotoxicity and consequently the neurodegeneration processes in the hippocampus.
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http://dx.doi.org/10.1016/j.pbb.2010.02.013DOI Listing
May 2010

Pharmacological and biochemical effects of Ginkgo biloba extract on learning, memory consolidation and motor activity in old rats.

Acta Neurobiol Exp (Wars) 2009 ;69(2):217-31

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland.

Effect of administration of the standardized extract of Ginkgo biloba leaves (EGb 761) on learning, memory and exploratory behavior was estimated in water maze and hole-board tests. Rats (18-month old) received for three months EGb 761 at doses: 50, 100 and 150 mg/kg b.w. per day. After completion of the behavioral experiment, concentrations of neurotransmitters were estimated in selected brain regions. ANOVA demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the control. The increased level of 5-hydroxytryptamine (5-HT) in the hippocampus and 5-HIAA (5-HT metabolite) in the prefrontal cortex correlated positively with the retention of spatial memory. Positive correlation between platform crossings in SE during the probe trial and neurotransmitter turnover suggest improvement of spatial memory. Long-term administration of Ginkgo biloba extract can improve spatial memory and motivation with significant changes in the content and metabolism of monoamines in several brain regions.
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September 2009

New hippocampal neurons are not obligatory for memory formation; cyclin D2 knockout mice with no adult brain neurogenesis show learning.

Learn Mem 2009 Jul 24;16(7):439-51. Epub 2009 Jun 24.

Laboratory of Molecular Neurobiology, Nencki Institute, Warsaw, Poland.

The role of adult brain neurogenesis (generating new neurons) in learning and memory appears to be quite firmly established in spite of some criticism and lack of understanding of what the new neurons serve the brain for. Also, the few experiments showing that blocking adult neurogenesis causes learning deficits used irradiation and various drugs known for their side effects and the results obtained vary greatly. We used a novel approach, cyclin D2 knockout mice (D2 KO mice), specifically lacking adult brain neurogenesis to verify its importance in learning and memory. D2 KO mice and their wild-type siblings were tested in several behavioral paradigms, including those in which the role of adult neurogenesis has been postulated. D2 KO mice showed no impairment in sensorimotor tests, with only sensory impairment in an olfaction-dependent task. However, D2 KO mice showed proper procedural learning as well as learning in context (including remote memory), cue, and trace fear conditioning, Morris water maze, novel object recognition test, and in a multifunctional behavioral system-IntelliCages. D2 KO mice also demonstrated correct reversal learning. Our results suggest that adult brain neurogenesis is not obligatory in learning, including the kinds of learning where the role of adult neurogenesis has previously been strongly suggested.
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http://dx.doi.org/10.1101/lm.1459709DOI Listing
July 2009

Effect of kindled seizures on rat behavior in water Morris maze test and amino acid concentrations in brain structures.

Pharmacol Rep 2006 Jan-Feb;58(1):75-82

Department of Experimental and Clinical Pharmacology, Medical University, Krakowskie Przedmieście 26/28, PL 00-927 Warszawa, Poland.

The effects of kindled seizures elicited by repeated pentetetrazole (PTZ) injections, on learning and memory in the Morris water maze test and on concentration of brain amino acids, were examined in rats. It was found that kindled seizures (a model of temporal lobe epilepsy) produced a profound decrease in learning and memory accompanied by a selective and long-lasting decrease in hippocampal and striatal concentration of glutamate, glycine and alanine in the striatum (ex vivo measurement). The concentrations of histamine, serine and gamma-aminobutyric acid (GABA) were not selectively affected by kindling. Alower concentration of glutamate and N-methyl-D-aspartate (NMDA) receptor co-agonists in the striatum (glycine and alanine) indicates the general malfunction of the brain glutamatergic system. It is suggested that a selective decrease in hippocampal glutamate concentration may account for deterioration in learning and memory processes in kindled rats, considering the important role of this neurotransmitter in the cognitive processes (e.g. in the long-term potentiation), and the key contribution of the hippocampus to the spatial memory. The intrinsic mechanisms of the reported behavioral effects may involve neuronal damage in the brain limbic structures, secondary to seizure-induced ischemia and hypoxia.
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November 2006

Long term administration of Hypericum perforatum improves spatial learning and memory in the water maze.

Biol Pharm Bull 2002 Oct;25(10):1289-94

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Poland.

The aim of the present study is to investigate the effects of long-term Hypericum perforatum treatment on spatial learning and memory in rats. Hypericum preparation (HP) standardized to 0.3% hypericin content was administered orally for 9 weeks in doses of 4.3 and 13 microg/kg corresponding to therapeutic dosages in humans of 0.3 and 0.9 mg of total hypericins daily. A Morris water maze paradigm was used. The mean escape latency over 4 d for the Control group (21.9 s) and HP 4.3 group (21.7 s) was significantly greater than the latency of the HP 13 group (15.8s). In the probe trial on day 5, the HP 13 group crossed the correct annulus in the SE quadrant more often (4.5) than the other groups: Con (2.4) and HP 4.3 (3.1). After completion of the behavioral experiment, the regional brain concentrations of monoamines and metabolites were estimated in selected brain regions, i.e. prefrontal cortex, hippocampus and hypothalamus. Analysis of variance (ANOVA) demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the Control. The increased 5-hydroxytryptamine (5-HT) levels in the prefrontal cortex correlated positively with the retention of spatial memory. These findings show that the long-term administration of Hypericum perforatum can improve learning and spatial memory with significant changes in the content of monoamines in several brain regions.
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http://dx.doi.org/10.1248/bpb.25.1289DOI Listing
October 2002