Ilona Joniec-Maciejak

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

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.

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

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 Parkinsons 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.

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

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.

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

BACKGROUND Parkinsons 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.

Paracetamol—The outcome on neurotransmission and spatial learning in rats

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.

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

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.

Paracetamol impairs the profile of amino acids in the rat brain

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.

Developmental exposure to paracetamol causes biochemical alterations in medulla oblongata.

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.

Cerebellar level of neurotransmitters in rats exposed to paracetamol during development

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).

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

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.