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@#Objective To investigate the protective effect of insulin-like growth factor-1 (IGF-1) on 6-hydroxy dopamine (6-OHDA) induced oxidative damage in PC-12 cells. Methods PC12 cells were treated with 6-OHDA (concentrations of 25, 50, 100, 150 and 200 μmol/L). In order to select the optimal experimental concentration and treatment time, the activity of PC12 cells was detected by MTT at different time points of 12 h, 24 h and 48 h after treatment. PC12 cells were divided into three groups: control group, 6-OHDA group and IGF-1+6-OHDA group. The activity of PC12 cells was detected by MTT assay. Reactive oxygen species (ROS) level of PC12 cells was detected by immunofluorescence staining, and apoptosis was detected by Hoechst33342 / PI double staining method. Results With the increased concentration and the prolongation of the action time of 6-OHDA, the activity of PC12 cells decreased gradually. The concentration of 150 μmol/L and action time of 24 h of 6-OHDA were selected as the optimal experimental concentration and observation time for this study. Compared with 6-OHDA group, the activity of PC12 cells increased, the expression level of ROS and the apoptosis decreased in IGF-1+6-OHDA group. Conclusion IGF-1 pretreatment can reduce 6-OHDA induced oxidative damage and apoptosis of PC12 cells, also can increase cell activity, which can provide a potential strategy for the prevention and treatment of Parkinson’s disease.
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Objetivos : Evaluar el efecto neurotóxico del extracto acuoso de boldo (Peumus boldus) en un modelo experimental. Materiales y métodos. Se diseñó un experimento, que incluyó 20 ratas macho Holtzman de 250 ± 15 gr, distribuidas aleatoriamente en cuatro grupos: el control negativo recibió solución salina (SS) por vía oral (VO), el control positivo que recibió 6-hidroxidopamina por vía intracraneal (VIC) y SS por VO, el grupo experimental 1 recibió extracto acuoso de boldo (EAB) por VO y el grupo experimental 2 recibió 6-hidroxidopamina por VIC y EAB por VO, en todos los casos durante 21 días. Se realizó una evaluación neurológica, la cual tuvo tres componentes: a) clínico, evaluado con el test de rotarod, b) bioquímico, mediante la determinación de niveles séricos de ácido úrico, y c) histopatológico, por inmunohistoquímica para neuronas dopaminérgicas de sustancia negra. Se empleó la prueba de Kruskal Wallis y el test de Dunn para evaluar las diferencias entre los grupos. Resultados. Se encontró disminución significativa en el tiempo de latencia del test de rotarod entre los grupos control negativo y control positivo (p<0,01), control negativo y experimental 1 (p=0,09), control negativo y experimental 2 (p<0,01), control positivo y experimental 1 (p=0,04), y experimental 1 y 2 (p=0,09). En la determinación de ácido úrico no hubo diferencia significativa intergrupal. En el conteo neuronal hubo depleción de neuronas dopaminérgicas totales, pero sin diferencia intergrupal. Conclusiones. Se evidencio un efecto neurotóxico del extracto acuoso de boldo en ratas macho de la cepa Holtzman a nivel clínico.
Objectives. To assess the neurotoxic effect of the aqueous extract of boldo (Peumus boldus) in an experimental model. Materials and methods. 20 male Holtzman rats of 250 ± 15 g were randomized into four groups: the negative control received saline solution (SS) orally (PO), the positive control received 6-hydroxydopamine intracranially (IC) and SS by PO. Experimental group 1 received aqueous extract of boldo (AEB) by PO, and experimental group 2 received 6-hydroxydopamine intracranially and AEB by PO. The experiment lasted 21 days. A neurological assessment was performed which had three components: a) clinical, evaluated with the rotarod test, b) biochemical, by measuring serum levels of uric acid, and c) histopathology, by immunohistochemistry for substantia nigra dopaminergic neurons. The Kruskal Wallis test and the Dunn test were used to assess differences between groups. Results. A significant decrease was found in the latency time of the rotarod test between the negative and positive control group (p<0.01), negative control and experimental 1 (p=0.09), negative control and experimental 2 (p<0.01), positive control and experimental 1 (p=0.04), and experimental 1 and 2 (p=0.09). There was no significant intergroup difference in the identification of uric acid. There was a depletion of the total dopaminergic neurons in the neuronal count, without intergroup difference. Conclusions. A neurotoxic effect of aqueous extract of boldo was recognized at a clinical level in Holtzman male rats.
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Animals , Male , Rats , Neurotoxicity Syndromes/etiology , Peumus , Plant Extracts/toxicity , Disease Models, Animal , Rats, Sprague-DawleyABSTRACT
Objective To explore the mechanism through which nicotine protects dopaminergic neurons against 6-OHDA toxicity in SD rat. Methods Rats received nicotine or saline treatment (two doses tested,0. 2 rag/ kg and 2 rag/ kg, 5 injections i.p. per day at 2-h intervals). On day 8after the treatment, a single injection of 20μg of 6-OHDA was administered into right striatum.Nicotine or saline was administered continuously daily until animals were killed. The dopaminergic neurons and CD3, CD4 and CDS-positive lymphocytes were analyzed quantitatively using immunohistochemistry. Microglia activation was quantified by IBA1 immunofluorescence. Results The loss of dopaminergic neurons induced by 6-OHDA in the substantia nigra was significantly less severe in the nicotine treatment group (at both 0. 2 and 2 mg/kg groups) than that in the saline treated group. In the striatum, we observed that the number of CD3, CD4 and CD8-positive lymphocytes reduced significantly in the nicotine treated animals as compared to saline controls. Otherwise, nicotine inhibited CD4 and CD8-positive lymphocytes infiltration equivalently. Quantitative immunofluorescenee analysis indicated the microglia activation was inhibited obviously in nicotine treatment. Conclusions Our data suggest that nicotine may have a neuroprotective effect against dopaminergic lesion induced by 6-OHDA by inhibiting the inflammation.
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280r/40min). So the PD model was regarded eligible. In the site of lesion in SN, the number and volume of dobaminergic neurons were decreased, and the tissue structure of SN became indistinct, the levels of dopamine (DA), dihydroxyphenylaceticacid (DOPAC), homovanillicacid (HVA) 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleaceticacid (5-HIAA) were more conspicuously reduced than that in uninjured side. TH-immunoreactive cells of substantia nigra compact part were lessened obviously on injured side. The abnormal rotatory behavior of PD rats did not spontaneously disappear during 10 months of continuous observation. Conclusion The PD rat model, which is reproduced by injecting 6-OHDA to selectively destroy dopaminergic neurons in the substantia nigra of rat, is stable and reliable, and demonstrated similar primary pathological changes of PD.
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Objective To study the influence of nitric oxide synthase (NOS) inhibitor in a rat model of Parkinson’s disease. Methods Hemi-Parkinsonism rat model was established by stereotaxic 6-hydroxydopamine (6-OHDA) lesions in striatum in which nitric oxide synthase (NOS) was inhibited by L-Nitro-Arginine (L-NNA) and apomorphin-induced rotational behavior was measured. The immunohistochemical staining method was used to observe the change of striatal nNOS-positive neurons and nigral tyrosine hydroxylase(TH)-positive neurons. Results L-NNA dramatically protected 6-OHDA-injected rats against indices of severe injury to the nigrostriatal dopaminergic pathway, including decreases in numbers of TH-positive nigral neurons and rotational behavior. The nNOS-positive neurons showed no changes in numbers. Conclusions These results indicate that NO might mediate, in part, 6-OHDA-induced neurotoxicity and nNOS-positive neurons might resist the 6-OHDA neurotoxicity. NOS inhibitor may play a role in the protection of 6-OHDA neurons.
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AIM: To observe the relationship between noradrenaline and the synaptic configuration in rat hippocampus CA3 area. METHODS: Noradrenergic system injured models were produced by injecting 6-hydroxydopamine into rats' bilateral dorsal noradrenergic bundle. Then Y-type maze tests and elicitation of P3-like were carried out respectively before and after the model was established. The parameters of synaptic configuration in the hippocampus CA3 areas were also analyzed quantitatively. RESULTS: The decreases in the thickness of postsynaptic density material, the curvature of synaptic interface and the occurrence of perforated synapses, and the increase in the width of synaptic cleft were observed. CONCLUSION: The normal noradrenalin level in hippocampus is necessary to maintain the normal synaptic interface ultrastructure in hippocampus CA3 area.
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Arginine-8-vasopressin (AVP) could promote the acquisition of shuttle-box passive avoidance behavior and delay the extinction of the behavior when injected into the hippocampus of rats.Intrahippocampal injection of 6-hydroxydopamine (6-OHDA) prevented AVP from enhancing memory.The authors had also observed that AVP could accelerate the degradation of cate-cholamine in the hippocampus when the contents of monoamine transmitters and their metabolites were analyzed with high-performance liquid chromatography and electrochemical detection. These facts suggest that vasopressin promotes the shuttle-box passive avoidance behavior in rats,strcnthens long-term memory as well as short-term memory,and exerts its effect on memory through its enhancing the degradation of norepinephrine and/or dopamine in the hippocampus.