Publications by authors named "Ilona Joniec-Maciejak"

27 Publications

  • Page 1 of 1

Deficiency of Biogenic Amines Modulates the Activity of Hypoglossal Nerve in the Reserpine Model of Parkinson's Disease.

Cells 2021 Mar 2;10(3). Epub 2021 Mar 2.

Department of Respiration Physiology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland.

The underlying cause of respiratory impairments appearing in Parkinson's disease (PD) is still far from being elucidated. To better understand the pathogenesis of respiratory disorders appearing in PD, we studied hypoglossal (HG) and phrenic (PHR) motoneuron dysfunction in a rat model evoked with reserpine administration. After reserpine, a decrease in the baseline amplitude and minute HG activity was noted, and no depressive phase of the hypoxic ventilatory response was observed. The pre-inspiratory time of HG activity along with the ratio of pre-inspiratory time to total respiratory cycle time and the ratio of pre-inspiratory to inspiratory amplitude were significantly reduced during normoxia, hypoxia, and recovery compared to sham rats. We suggest that the massive depletion of not only dopamine, but above all noradrenaline and serotonin in the brainstem observed in our study, has an impact on the pre-inspiratory activity of the HG. The shortening of the pre-inspiratory activity of the HG in the reserpine model may indicate a serious problem with maintaining the correct diameter of the upper airways in the preparation phase for inspiratory effort and explain the development of obstructive sleep apnea in some PD patients. Therapies involving the supplementation of amine depletion other than dopamine should be considered.
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http://dx.doi.org/10.3390/cells10030531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001069PMC
March 2021

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

Respiratory pattern and phrenic and hypoglossal nerve activity during normoxia and hypoxia in 6-OHDA-induced bilateral model of Parkinson's disease.

J Physiol Sci 2020 Mar 11;70(1):16. Epub 2020 Mar 11.

Department of Respiration Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5, 02-106, Warsaw, Poland.

Respiratory disturbances present in Parkinson's disease (PD) are not well understood. Thus, studies in animal models aimed to link brain dopamine (DA) deficits with respiratory impairment are needed. Adult Wistar rats were lesioned with injection of 6-hydroxydopamine (6-OHDA) into the third cerebral ventricle. Two weeks after hypoxic test was performed in whole-body plethysmography chamber, phrenic (PHR) and hypoglossal (HG) nerve activities were recorded in normoxic and hypoxic conditions in anesthetized, vagotomized, paralyzed and mechanically ventilated rats. The effects of activation and blockade of dopaminergic carotid body receptors were investigated during normoxia in anesthetized spontaneously breathing rats. 6-OHDA injection affected resting respiratory pattern in awake animals: an increase in tidal volume and a decrease in respiratory rate had no effect on minute ventilation. Hypoxia magnified the amplitude and minute activity of the PHR and HG nerve of 6-OHDA rats. The ratio of pre-inspiratory to inspiratory HG burst amplitude was reduced in normoxic breathing. Yet, the ratio of pre-inspiratory time to total time of the respiratory cycle was increased during normoxia. 6-OHDA lesion had no impact on DA and domperidone effects on the respiratory pattern, which indicate that peripheral DA receptors are not affected in this model. Analysis of monoamines confirmed substantial striatal depletion of dopamine, serotonin and noradrenaline (NA) and reduction of NA content in the brainstem. In bilateral 6-OHDA model changes in activity of both nerves: HG (linked with increased apnea episodes) and PHR are present. Demonstrated respiratory effects could be related to specific depletion of DA and NA.
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http://dx.doi.org/10.1186/s12576-020-00743-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066294PMC
March 2020

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

Effects of α-Synuclein Monomers Administration in the Gigantocellular Reticular Nucleus on Neurotransmission in Mouse Model.

Neurochem Res 2019 Apr 13;44(4):968-977. Epub 2019 Feb 13.

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

The aim of the study was to examine the Braak's hypothesis to explain the spreading and distribution of the neuropathological changes observed in the course of Parkinson's disease among ascending neuroanatomical regions. We investigated the neurotransmitter levels (monoamines and amino acid concentration) as well as tyrosine hydroxylase (TH) and transglutaminase-2 (TG2) mRNA expression in the mouse striata (ST) after intracerebral α-synuclein (ASN) administration into gigantocellular reticular nucleus (Gi). Male C57BL/10 Tar mice were used in this study. ASN was administrated by stereotactic injection into Gi area (4 μl; 1 μg/μl) and mice were decapitated after 1, 4 or 12 weeks post injection. The neurotransmitters concentration in ST were evaluated using HPLC detection. TH and TG2 mRNA expression were examined by Real-Time PCR method. At 4 and 12 weeks after ASN administration we observed decrease of DA concentration in ST relative to control groups and we found a significantly higher concentration one of the DA metabolites-DOPAC. At these time points, we also noticed the increase in DA turnover determined as DOPAC/DA ratio. Additionally, at 4 and 12 weeks after ASN injection we noted decreasing of TH mRNA expression. Our findings corresponds with the Braak's theory about the presence of the first neuropathological changes within brainstem and then with time affecting higher neuroanatomical regions. These results obtained after administration of ASN monomers to the Gi area may be useful to explain the pathogenesis of Parkinson's disease.
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http://dx.doi.org/10.1007/s11064-019-02732-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437297PMC
April 2019

Octanoic acid prevents reduction of striatal dopamine in the MPTP mouse model of Parkinson's disease.

Pharmacol Rep 2018 Sep 25;70(5):988-992. Epub 2018 Apr 25.

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

Background: Parkinson's disease (PD) is a progressive neurodegenerative process leading to the loss of dopaminergic neurons and their projections. 1-methyl-4-phenol-1,2,5,6-tetrahydropyridine (MPTP) toxicity is a well-recognized animal model of PD. It is suggested that the impairment of mitochondrial function in the substantia nigra plays an important role in both the onset and the progression of PD. Octanoic acid (C8), a fatty acid that is the main constituent of the medium-chain triglyceride ketogenic diet, increases the metabolic activity of mitochondria; hence, it seemed interesting to investigate whether C8 exhibits neuroprotective effects in the MPTP model of PD and whether it affects mitochondria function in the striatum.

Methods: Therefore, we examined the possible protective effects of C8 in the mouse model of PD induced by MPTP. For this purpose, changes in the concentration of DA and its metabolites were determined. In addition, we investigated whether expression levels of PGC-1α and the PEPCK enzyme, markers of mitochondrial activity, are altered by C8.

Results: In this study, we observed for the first time that acute and, in particular, repeated administrations of C8 significantly reduced the impairment of dopaminergic neurotransmission in the striatum evoked by MPTP administration and resulted in a marked increase in PGC-1α expression and in both forms of PEPCK.

Conclusions: These results indicate that the C8 leads to an inhibition of the neurodegenerative processes seen after MPTP administration. Our results suggest that a probable mechanism of the neuroprotective action of C8 is related to an increase in metabolic activity in striatal mitochondria.
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http://dx.doi.org/10.1016/j.pharep.2018.04.008DOI Listing
September 2018

Octanoic acid prevents reduction of striatal dopamine in the MPTP mouse model of Parkinson's disease.

Pharmacol Rep 2018 Oct 25;70(5):988-992. Epub 2018 Apr 25.

Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology (CePT), Warszawa, Poland; Department of Neurochemistry, Institute of Psychiatry and Neurology, Warszawa, Poland.

Background: Parkinson's disease (PD) is a progressive neurodegenerative process leading to the loss of dopaminergic neurons and their projections. 1-methyl-4-phenol-1,2,5,6-tetrahydropyridine (MPTP) toxicity is a well-recognized animal model of PD. It is suggested that the impairment of mitochondrial function in the substantia nigra plays an important role in both the onset and the progression of PD. Octanoic acid (C8), a fatty acid that is the main constituent of the medium-chain triglyceride ketogenic diet, increases the metabolic activity of mitochondria; hence, it seemed interesting to investigate whether C8 exhibits neuroprotective effects in the MPTP model of PD and whether it affects mitochondria function in the striatum.

Methods: Therefore, we examined the possible protective effects of C8 in the mouse model of PD induced by MPTP. For this purpose, changes in the concentration of DA and its metabolites were determined. In addition, we investigated whether expression levels of PGC-1α and the PEPCK enzyme, markers of mitochondrial activity, are altered by C8.

Results: In this study, we observed for the first time that acute and, in particular, repeated administrations of C8 significantly reduced the impairment of dopaminergic neurotransmission in the striatum evoked by MPTP administration and resulted in a marked increase in PGC-1α expression and in both forms of PEPCK.

Conclusions: These results indicate that the C8 leads to an inhibition of the neurodegenerative processes seen after MPTP administration. Our results suggest that a probable mechanism of the neuroprotective action of C8 is related to an increase in metabolic activity in striatal mitochondria.
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http://dx.doi.org/10.1016/j.pharep.2018.04.008DOI Listing
October 2018

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

The phosphodiesterase inhibitor, ibudilast, attenuates neuroinflammation in the MPTP model of Parkinson's disease.

PLoS One 2017 28;12(7):e0182019. Epub 2017 Jul 28.

2nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland.

Background/aims: Since the degeneration of the nigrostriatal dopaminergic pathway in Parkinson's disease (PD) is associated with the inflammation process and decreased levels of cyclic nucleotides, inhibition of up-regulated cyclic nucleotide phosphodiesterases (PDEs) appears to be a promising therapeutic strategy. We used ibudilast (IBD), a non-selective PDE3,4,10,11 inhibitor, due to the abundant PDE 4 and 10 expression in the striatum. The present study for the first time examined the efficacy of IBD in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD.

Methods: IBD [0, 20, 30, 40, or 50 mg/kg] was injected b.i.d. subcutaneously for nine days to three-month-old male C57Bl/10Tar mice, beginning two days prior to MPTP (60 mg/kg) intoxication. High-pressure liquid chromatography, Western blot analysis, and real time RT-PCR methods were applied.

Results: Our study demonstrated that chronic administration of IBD attenuated astroglial reactivity and increased glial cell-derived neurotrophic factor (GDNF) production in the striatum. Moreover, IBD reduced TNF-α, IL-6, and IL-1β expression.

Conclusion: IBD had a well-defined effect on astroglial activation in the mouse model of PD; however, there was no protective effect in the acute phase of injury. Diminished inflammation and an increased level of GDNF may provide a better outcome in the later stages of neurodegeneration.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182019PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533435PMC
October 2017

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

The effect of α-synuclein on gliosis and IL-1α, TNFα, IFNγ, TGFβ expression in murine brain.

Pharmacol Rep 2017 Apr 9;69(2):242-251. Epub 2016 Nov 9.

Department of Experimental and Clinical Pharmacology, Medical University of Warszawa, Centre for Preclinical Research and Technology CePT, Warszawa, Poland; 2nd Department of Neurology, Institute of Psychiatry and Neurology, Warszawa, Poland. Electronic address:

Background: Alpha - synuclein (ASN) is the principal component of Lewy pathology and strongly influences on the pathogenesis of Parkinson's disease (PD). The increased level of ASN protein causes microglial response. The reactive microglial cells may actively participate in the damaging of dopaminergic neurons. The data suggests that ASN accumulation in astrocytes might damage these cells in the substantia nigra pars compacta (SN) and promotes degeneration of dopaminergic neurons in SN. We examined the potential role of recombinant ASN monomers as a major pathogenic factor causing the inflammatory response in the central nervous system.

Methods: Mice were bilaterally infused by human ASN monomers into the striatum (ST) or SN (single treatment was 4μg/structure, 8μg per brain) and decapitated after 1, 4 or 12 weeks post injection. The changes in the level of inflammatory factors in ST were evaluated using Real-Time PCR and Western Blot method. The analysis of morphological changes of glial cells was performed by immunohistochemical staining.

Results: We observed a strong activation of microglia cells in ST and increased expression of striatal interleukin 1α, tumor necrosis factor alpha and interferon gamma after ASN injection into the ST. We noticed an increase in striatal glial fibrillary acidic protein mRNA level 4 weeks after ASN injection into the ST. Injection of ASN into the SN led to an increase of striatal transforming growth factor beta mRNA level and has no influence on striatal glial fibrillary acidic protein mRNA level.

Conclusion: Our results suggest that both the microglia activation and supressing astrocytes play a crucial role in ASN-related dopaminergic neurotoxicity.
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http://dx.doi.org/10.1016/j.pharep.2016.11.003DOI 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

Lactate Formation in Primary and Metastatic Colon Cancer Cells at Hypoxia and Normoxia.

Cell Biochem Funct 2016 Oct 16;34(7):483-490. Epub 2016 Aug 16.

Chair and Department of Biochemistry, Medical University of Warsaw, Warsaw, Poland.

High glucose consumption and lactate synthesis in aerobic glycolysis are a hallmark of cancer cells. They can form lactate also in glutaminolysis, but it is not clear how oxygen availability affects this process. We studied lactate synthesis at various oxygen levels in human primary (SW480) and metastatic (SW620) colon cancer cells cultured with L-Ser and/or L-Asp. Glucose and lactate levels were determined colorimetrically, amino acids by HPLC, expression of AST1-mRNA and AST2-mRNA by RT-PCR. In both lines glucose consumption and lactate synthesis were higher at 10% than at 1% oxygen, and lactate/glucose ratio was increased above 2.0 by L-Asp. AST1-mRNA expression was independent on oxygen and cell line, but AST2-mRNA was lower at hypoxia in SW480. We conclude that, in both cell lines at 1% hypoxia, lactate is formed mainly from glucose but at 10% normoxia also from L-Asp. At 10% normoxia, lactate synthesis is more pronounced in primary than metastatic colon cancer cells.
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http://dx.doi.org/10.1002/cbf.3211DOI Listing
October 2016

Exogenous α-Synuclein Monomers Alter Dopamine Metabolism in Murine Brain.

Neurochem Res 2016 Aug 9;41(8):2102-9. Epub 2016 May 9.

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

Alpha-synuclein (ASN) is a small presynaptic protein which is the major component of Lewy bodies-the histological hallmark of Parkinson's disease. Among many functions, ASN plays an important role in regulation of dopaminergic system by controlling dopamine concentration at nerve terminals. An abnormal structure or excessive accumulation of ASN in the brain can induce neurotoxicity leading to the dopaminergic neurodegeneration. To date, several transgenic mouse lines overexpressing ASN have been generated and there are several studies using injections of ASN fibrils into the murine brain. However, still is little known about the effects of exogenously applied ASN monomers on dopaminergic neurotransmission. In this study we investigated the influence of cerebral injection of human ASN on dopaminergic system activity. We have demonstrated that a single injection of ASN monomers into the substantia nigra pars compacta or striatum is sufficient to affect dopaminergic neurotransmission in murine nigro-striatal system.
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http://dx.doi.org/10.1007/s11064-016-1923-zDOI Listing
August 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

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

The influence of AAV2-mediated gene transfer of human IL-10 on neurodegeneration and immune response in a murine model of Parkinson's disease.

Pharmacol Rep 2014 Aug 8;66(4):660-9. Epub 2014 Apr 8.

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

Background: The aim of this study was to examine the effect of AAV2-hIL-10 (vector containing cDNA for human interleukin 10) on dopaminergic system activity (measured as DA levels and TH mRNA expression in mouse striata), and other monoamine and amino acid neurotransmitters concentration as well as development of inflammatory processes (measured as TGF-β, IFN-γ and GFAP mRNA expression) in a murine MPTP neurotoxicant model of Parkinson's disease.

Methods: Male C57BL/6 mice 12 months-old were used in this study. AAV2-hIL-10 vector was bilaterally administered into striatum at 14, 21 or 28 days prior to MPTP intoxication. Animals were sacrificed at 7 days following MPTP injection. The expression of hIL-10 (human interleukin 10) was examined by ELISA. Striatal monoamine and amino acid neurotransmitters were measured by HPLC method. TH, TGF-β, IFN-γ and GFAP mRNA expression was examined by RT-PCR method.

Results: MPTP treatment dramatically reduced DA levels and decreased TH mRNA expression in mouse striata, effects that were significantly impeded by AAV2-hIL-10 administration prior to MPTP intoxication. AAV2-hIL-10 infusion increased IFN-γ, TGF-β and GFAP mRNA expression.

Conclusions: Our data suggest that the transfer of AAV2-hIL-10 into the striatum may play a neuroprotective role in the mouse MPTP model of PD and these effects are mediated by the anti-inflammatory action of IL-10.
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http://dx.doi.org/10.1016/j.pharep.2014.03.008DOI Listing
August 2014

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

Effect of human interleukin-10 on the expression of nitric oxide synthases in the MPTP-based model of Parkinson's disease.

Pharmacol Rep 2013 ;65(1):44-9

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

Background: Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder. The degeneration of the nigro-striatal pathway has been linked with the inflammatory process accompanied by the robust up-regulation of the nitric oxide synthase (NOS) and production of the neurotoxic level of nitric oxide (NO). One of the therapeutic strategies of PD is based on the reduction of the detrimental neuroinflammatory markers in the lesioned nigro-striatal pathway. In this study we have investigated the neuroprotective effect of the cerebral infusion of recombinant adeno-associated viral vector, expressing the gene for human interleukin-10 (AAV2-hIL-10) in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). It is known that IL-10 is a potent anti-inflammatory cytokine that limits the inducible nitric oxide synthase (iNOS) gene expression.

Methods: The striatal iNOS, neuronal nitric oxide synthase (nNOS) and tyrosine hydroxylase (TH) protein expression was evaluated by immunoblot analysis.

Results: The intracerebral injection of the AAV2-hIL-10, before the lesion, induced the upregulation of the striatal TH protein, depleted by MPTP intoxication. This AAV2-hIL-10-induced increase of TH level was associated with the suppression of iNOS protein expression in the lesioned striatum.

Conclusion: The results revealed protective properties of AAV2-hIL-10.
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http://dx.doi.org/10.1016/s1734-1140(13)70962-9DOI Listing
October 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