The pathological process of neurodegeneration is accompanied by an inflammatory reaction that is believed to contribute to the pathogenesis of neurodegenerative diseases. The aim of our study was to evaluate the influence of autoimmune reaction induced by post-traumatic vaccination with myelin self-antigen on spontaneous regeneration of dopaminergic neurons, injured with MPTP. C57BL mice were intoxicated with 40 mg/kg MPTP and seven days later immunized with MOG 35-55 peptide in CFA. On 7th day following intoxication, the MPTP treated mice showed decrease of dopamine level by 63% as compared to the control mice. However, starting from the 14th day following intoxication, a spectacular increase of dopamine content was observed. Immunization with MOG resulted in statistically significant reduction of the increase in striatum as compared to non-immunized animals, and was lower by 23%, 17% and 15% on days 14, 28 and 50, respectively. Our results show suppressive influence of autoimmune reaction induced after injury on regeneration of dopamine cells intoxicated with MPTP.
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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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The inflammatory reaction and oxidative stress has been linked with PD. Proinflammatory cytokines promote neurodegeneration or neuroprotection in different animal models. In addition, these cytokines have been reported to increase iNOS expression. With the RT-PCR method we evaluated mRNA levels for IL1beta, IL6, TNF, IFN gamma, IL-10 and iNOS in the striatum of C57BL/6 mice after MPTP intoxication. The IL1beta mRNA expression rapidly increased, nad peaked at 6 h. The first increase of mRNA for TNFalpha and INFgamma was noticed at 6-24 h and the second at the 7th day after MPTP intoxication. Two peaks of IL10 mRNA were seen, immediately (6 h) and at the 3rd day post MPTP injection. The peak of mRNA level for IL6 was observed at the 7th day. Expression of mRNA for iNOS peaked at 24 h, started decreasing on the 3rd day, but was still present till the 14th day Those findings suggest that cytokine network and iNOS may be involved in the development of immune changes accompanying degeneration of the nigrostriatal system.
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Many data suggest involvement of inflammation in neurodegeneration. However, the exact mechanisms of this cooperation are poorly understood. We have previously shown that induction of inflammatory reaction, both before and after injury of the striatum, affects regeneration of dopaminergic neurons. In the present research we studied the role of inflammatory reaction in non-injured striatum. We used myelin oligodendrocyte glycoprotein (MOG) 35-55 in complete Freund's adjuvant (CFA) to elicit experimental autoimmune encephalomyelitis (EAE) mice model. As determined by HPLC, striatal dopamine (DA) and serotonin levels in mice treated with either MOG 35-55 in CFA or CFA alone were significantly higher compared to vehicle-treated controls on 13th day after induction. The ratio of homovanilic acid/dopamine (HVA/DA) and 3, 4 dihydroxyphenylacetic acid/dopamine (DOPAC/DA) were significantly lower in the MOG and CFA groups on 13th day, indicating decreased DA metabolism. Noradrenaline (NA) concentration did not differ between groups. Moreover, the striatal mRNA IL-1beta and TNF-alpha levels were elevated during induction phase of EAE in both groups, as determined by RT-PCR. Our data indicate regulatory connection between dopaminergic and immune systems.
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