Curcumin protects nigral dopaminergic neurons by iron-chelation in the 6-hydroxydopamine rat model of Parkinson’s disease

Objective Curcumin is a plant polyphenolic compound and a major component of spice turmeric (Curcuma longa). It has been reported to possess free radical-scavenging, iron-chelating, and anti-inflammatory properties in dif- ferent tissues. Our previous study showed that curcumin protects MES23.5 dopaminergic cells from 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro. The present study aimed to explore this neuroprotective effect in the 6-OHDA-lesioned rat model of Parkinson’s disease in vivo. Methods Rats were given intragastric curcumin for 24 days. 6-OHDA lesioning was conducted on day 4 of curcumin treatment. Dopamine content was assessed by high-performance liquid chromatography with electrochemical detection, tyrosine hydroxylase (TH)-containing neurons by immunohistochemistry, and iron-containing cells by Perls’ iron staining. Results The dopamine content in the striatum and the number of TH-immunoreactive neurons decreased after 6-OHDA treatment. Curcumin pretreatment reversed these changes. Further studies demonstrated that 6-OHDA treatment increased the number of iron-staining cells, which was dramatically decreased by curcumin pretreatment. Conclusion The protective effects of curcumin against 6-OHDA may be attributable to the ironchelating activity of curcumin to suppress the iron-induced degeneration of nigral dopaminergic neurons.     

乙醇诱导大鼠骨髓间充质干细胞的凋亡机制

BACKGROUND: Previous studies demonstrated that ethanol can induce apoptosis in bone marrow mesenchymal stem cells (BMSCs), and decrease the number of osteoplasts and osteoclasts. However, the effect and mechanism of ethanol on apoptosis in BMSCs remains unclear. OBJECTIVE: To investigate the effect of ethanol on apoptosis in BMSCs of rats and their mitochondrial function and to evaluate the pathway associated with the regulation of Bcl-2 and Caspase-3. METHODS: BMSCs were isolated from Sprague-Dawley rats were treated with ethanol at doses of 0, 100, 200, 300, 400, 500, 600, 700, 800, 900 mmol/L for 24 hours. cytotoxic drug experiment was performed with MTT assay. BMSCs were treated with ethanol at doses of 0, 100, 200, 300, 400, 500 mmol/L for 6, 12, 24 hours, AnnexinV/PI flow cytometry of double label method was performed to detect the apoptosis and mitochondrial membrane potential, BMSCs were treated with ethanol at doses of 0, 427 mmol/L for 24 hours, the levels of Bcl-2 and Caspase-3 mRNA expression were determined by RT-PCR method. RESULTS AND CONCLUSION: MTT assay results showed that 50% concentration of inhibition (IC50) of BMSCs of rats grew in ethanol was 427 mmol/L. The results of Annexin V/PI assay indicated that the apoptosis rates of BMSCs and mitochondrial membrane potential were higher than that of untreated (0 mmol/L) group when time and dose of ethanol was increased (P < 0.05). Compared with 0 mmol/L group, the level of Bcl-2mRNA expression was decreased in 427 mmol/L group after 24 hours, but the caspase-3 mRNA expression was increased significantly by treatment at 427 mmol/L (P < 0.05). These results suggest that ethanol can induce apoptosis in BMSCs of SD rat, and the occurrence of apoptosis may be related to the mitochondrial membrane potential damage, mitochondrial dysfunction, bcl-2 and Caspase-3 activation.     

Ameliorative effects of human adipose tissue-derived mesenchymal stem cells on myelin basic protein-induced experimental autoimmune encephalomyelitis in Lewis rats

Mesenchymal stem cells have been previously shown to exert an immunomodulatory function.The present study sought to investigate the effects of multipotential human adipose tissue-derived mesenchymal stem cells(hAdMSCs) on disease progression and cytokine expression in Lewis rats with experimental autoimmune encephalomyelitis(EAE) induced by myelin basic protein.The duration of EAE paralysis in the group treated on day 7 postimmunization with 5 × 106 hAdMSCs was significantly reduced compared with the vehicle-treated controls and the 1 × 106 hAdMSC-treated group.The duration of EAE paralysis in the groups treated with 5 × 106 hAdMSCs on both day 1 and day 7 postimmunization was significantly reduced compared with the vehicle-treated controls and the groups treated with 5 × 106 hAdMSCs on both day 7 and day 10 postimmunization.The mRNA expression of interleukin-10 and indoleamine 2,3-dioxygenase was significantly decreased in the hAdMSC-treated group compared with the vehicle-treated group.These findings suggest that the ameliorative effects of hAdMSCs on EAE symptoms operate in a dose-and time-dependent manner and can be mediated in part by the ample production of anti-inflammatory cytokines.     

Radix Achyranthis Bidentatae improves learning and memory capabilities in ovariectomized rats

Kidney-tonifying recipe can reduce the accumulation of advanced glycation end products, prevent neuronal degeneration and improve cognitive functions in ovariectomized rats. Radix Achyranthis Bidentatae alcohol extracts may dose-dependently inhibit non-enzymatic saccharification in vitro. This study aimed to examine the effect of Radix Achyranthis Bidentatae on advanced glycation end products and on learning and memory capabilities in ovariectomized rats. Ovariectomized rats were treated with Radix Achyranthis Bidentatae alcohol extracts (containing 1.5 g/kg crude drug) or 0.1% aminoguanidine for 12 weeks and behavioral testing was performed with the Y-electrical maze. This test revealed that Radix Achyranthis Bidentatae and aminoguanidine could improve the learning and memory capabilities of ovariectomized rats. Results of competitive enzyme-linked immunosorbent assay showed that treatment with Radix Achyranthis Bidentatae or aminoguanidine reduced the accumulation of advanced glycation end products in the frontal cortex of ovariectomized rats, while increasing content in the blood and urine. Biochemical tests showed that treatment with Radix Achyranthis Bidentatae or aminoguanidine decreased superoxide dismutase activity in the serum and frontal cortex, and increased serum levels of glutathione peroxidase in ovariectomized rats. In addition, there was no apparent effect on malondialdehyde levels. These experimental findings indicate that Radix Achyranthis Bidentatae inhibits production of advanced glycation end products and its accumulation in brain tissue, and improves learning and memory capabilities in ovariectomized rats. These effects may be associated with an anti-oxidative action of the extract.     

Oxidative stress regulated heme-oxygenase-1 and glutathione S-transferase-m1 gene expression changes in cell lines exposed to melanins

To investigate the effects of oxidative stress on substantia nigra neuronal degeneration and death in patients with Parkinson’s disease, we treated neuroblastoma cells (SK-N-SH) and glioma cells with Fenton’s reagent, iron chelating agent, neuromelanin and dopamine melanin. We investigated the changes in expression of nine oxidative stress-related genes and proteins. The levels of mRNAs for heme-oxygenase-1 and glutathione S-transferase-m1 were significantly reduced in SK-N-SH cells exposed to oxidative stress, and increased in glial cells treated with deferoxamine. These results revealed that SK-N-SH neurons react sensitively to oxidative stress, which implies different outcomes between these two types of cells in the substantia nigra. Moreover, the influences of neuromelanin and dopamine melanin on cell function are varied, and dopamine melanin is not a good model for neuromelanin.     

Phenotypic and functional comparison of rat enteric neural crest-derived cells during fetal and early-postnatal stages

In our previous study,we showed that with increasing time in culture,the growth characteristics of enteric neural crest-derived cells(ENCCs)change,and that the proliferation,migration and neural differentiation potential of these cells in vitro notably diminish.However,there are no studies on the developmental differences in these characteristics between fetal and early-postnatal stages in vitro or in vivo.In this study,we isolated fetal(embryonic day 14.5)and postnatal(postnatal day 2)ENCCs from the intestines of rats.Fetal ENCCs had greater maximum cross-sectional area of the neurospheres,stronger migration ability,and reduced apoptosis,compared with postnatal ENCCs.However,fetal and postnatal ENCCs had a similar differentiation ability.Fetal and postnatal ENCCs both survived after transplant into a rat model of Hirschsprung’s disease.In these rats with Hirschsprung’s disease,the number of ganglionic cells in the myenteric plexus was higher and the distal intestinal pressure change was greater in animals treated with fetal ENCCs compared with those treated with postnatal ENCCs.These findings suggest that,compared with postnatal ENCCs,fetal ENCCs exhibit higher survival and proliferation and migration abilities,and are therefore a more appropriate seed cell for the treatment of Hirschsprung’s disease.This study was approved by the Animal Ethics Committee of the Second Affiliated Hospital of Xi’an Jiaotong University(approval No.2016086)on March 3,2016.     

尼古丁抑制脂多糖诱发的混合胶质细胞或小胶质细胞分泌白细胞介素6

Inflammation plays an important role in the pathogenesis of Parkinson’s disease (PD) through the over-activation of microglia. Epidemiological studies show that smoking is associated with a lower incidence of PD. This study hypothesized that the neuroprotective effect of nicotine is mediated by modulating the activation of microglia via cytokine release. This study found that nicotine pretreatment suppressed the lipopolysaccharide-induced inflammatory reaction in the nervous system, especially microglia activation and interleukin-6 production. The inhibitory effects of 100 μmol/L nicotine were stronger compared with 1 and 10 μmol/L nicotine. These findings indicate that nicotine significantly decreases the production of proinflammatory interleukin-6 in mixed glia or microglia-enriched cultures, and plays an inhibitory effect on the lipopolysaccharide-induced inflammatory reaction.     

Low dose of corticosterone treatment with exercise increases hippocampal cell proliferation, and improves cognition

Intermediate level of stress is beneficial for brain functions, whereas extreme low level or high level of stress is deleterious. We have previously shown that chronic exposure to high doses of corticosterone (CORT) suppressed hippocampal plasticity and physical exercise in terms of running counteracted the detrimental effects of CORT treatment. We aimed to study whether a mild stress, that mimicked by a treatment with low CORT dose, improved hippocampal plasticity in terms of hippocampal cell proliferation and dendritic remodeling, and to examine whether running with CORT treatment showed an additive effect on improving hippocampal plasticity. The rats were treated with 20 mg/kg CORT for 14 days with or without running, followed by Morris water maze test or forced swim test. The hippocampal proliferating cells was labeled by intraperitoneal injection of 5-bromo-2’-deoxyuridine. The dendritic morphology was analyzed using Golgi staining method. Treatment with 20 mg/kg CORT alone yielded a higher number of hippocampal cell proliferation and significantly increased dendritic branching compared to vehicle-treated non-runners, but had no behavioral effects. In contrast, CORT treatment with running showed an additive increase in hippocampal cell proliferation and dendritic remodeling that was associated with improved spatial learning and decreased depression-like behavior; however, there was no additive improvement in behavior compared to vehicle-treated runners. These findings suggest that mild stress does not always cause detrimental effect on the brain, and combining mild stress with running could promote hippocampal plasticity via inducing cell proliferation and dendritic remodeling.     

Effects of anaesthetics on the loss of nigrostriatal dopaminergic neurons by 6-hydroxydopamine in rats

Summary. Various studies use ketamine/xylazine, fentanyl/medetomidine, etorphine/methotrimeprazine, and isoflurane anaesthesia for creating the 6-hydroxydopamine (6-OHDA)-lesion rat model of Parkinson’s disease. As these anaesthetics are known to modulate uptake and turnover of dopamine and that 6-OHDA-induced neurotoxicity is also dependents on uptake/turnover, we studied the effects of these anaesthetics on the extent of nigrostriatal dopaminergic damage caused by 6-OHDA. Infusion of 8 μg of 6-OHDA into the medial forebrain bundle significantly reduced the numbers of dopaminergic cells in nigra and striatal concentrations of dopamine in animals anaesthetized with fentanyl/medetomidine, etorphine/methotrimeprazine and isoflurane but not with ketamine/xylazine. In the latter group, however, increasing the dose of 6-OHDA to 10 and 12 μg resulted in a moderate (15 and 29%), but significant loss of dopaminergic cells. A severe loss of dopaminergic cells (59% and 81%) was seen with these doses in isoflurane-anaesthetized animals, but with only 8 μg in etorphine/methotrimeprazine-anaesthetized animals. Thus, these results suggest that the extent of nigrostriatal dopaminergic neuronal loss with 6-OHDA seems to be influenced by anaesthetic used during the surgery.     

还原型谷胱甘肽拮抗6-OHDA对骨髓基质细胞的毒性作用

目的:探讨6-羟基多巴胺(6-OHDA)对骨髓基质细胞(BMSCs)的毒性作用及还原型谷胱甘肽(GSH)对其的拮抗作用。方法:取体重60～90g的SD大鼠股骨、胫骨及肱骨BMSCs,体外培养至传3代。采用MTT法检测不同剂量6-OHDA对BMSCs的毒性作用,相同条件下同时检测GSH的细胞保护作用。结果:MTT显示GSH可使传3代BMSCs活性升高(P<0.05);6-OHDA可使传3代BMSCs的活性下降(P<0.05);GSH干预能提高6-OHDA作用后的传3代BMSCs的活性(P<0.05)。结论:一定剂量的6-OHDA对BMSCs具有毒性作用,GSH能够明显拮抗6-OHDA对BMSCs的毒性作用。     

还原型谷胱甘肽诱导大鼠骨髓基质细胞GFAPmRNA及蛋白表达变化

目的：研究还原型谷胱甘肽（GSH）对大鼠骨髓基质细胞（BMSCs）胶质纤维酸性蛋白（GFAP）mRNA及蛋白表达的影响。方法：传3代骨髓基质细胞随机分为GSH诱导组和对照组。GSH诱导组加入10mmol·L^-1GSH20μL,对照组加入生理盐水20UL,两组使用的培养基和处理过程相同。于加入GSH和生理盐水后6、12和24h观察记录细胞的生存情况及细胞的形态变化。采用实时荧光定量PCR和Westernblot法检测各组诱导后细胞GFAPmRNA及蛋白表达水平的变化。结果：经GSH诱导后BMSCs形态发生明显改变,GSH诱导组GFAPmRNA及蛋白表达水平显著高于对照组（P〈0．05）,以诱导12h后变化最为明显。结论：BMSCs经GSH诱导后GFAPmRNA及蛋白表达量显著增多。     

还原型谷胱苷肽治疗帕金森病大鼠模型的实验研究

目的观察还原型谷胱苷肽(GSH)治疗帕金森病(PD)大鼠模型的疗效。方法35只SD大鼠采用内侧前脑束注射6-羟多巴胺(6-OHDA)制作偏侧PD模型。术后第6周根据阿朴吗啡旋转试验将模型鼠分为部分PD组和完全PD组,各组再随机分为GSH亚组和对照亚组,并分别给予GSH或生理盐水腹腔注射,每日1次,共4周。治疗后第2周、4周、6周、8周进行阿朴吗啡旋转试验。结果共有27只大鼠制模成功,13只为部分PD模型,14只为完全PD模型;部分PD GSH亚组治疗后第4周、6周、8周阿朴吗啡旋转试验每分钟旋转次数较治疗前及相应的对照亚组显著减少(P<0.05~0.01);完全PD GSH亚组较治疗前及相应的对照亚组无显著变化。结论GSH治疗6-OHDA所致的部分PD大鼠模型有效,对完全PD大鼠模型无效。     

Effect of manipulating central catecholamines on puberty and the surge of luteinizing hormone and gonadotropin releasing hormone induced by pregnant mare serum gonadotropin in female rats

We have investigated the effect of manipulating central catecholamines on the timing of puberty (as assessed by vaginal opening) in female rats and the surge of luteinizing hormone (LH) and gonadotropin releasing hormone (GnRH) induced by pregnant mare serum gonadotropin (PMSG) in immature female rats. Manipulation of the catecholamines was carried out with either 6-hydroxydopamine (6-OHDA) administered with or without either desipramine (DMI) or pargyline, orα-methyl-p-tyrosine (α-MPT).The neonatal administration of 6-OHDA delayed puberty, an effect which was potentiated by pretreatment with DMI and was associated with a reduction in the rate of body growth. Catecholamine fluorescence in animals aged 60–65 days that had been treated with DMI followed by 6-OHDA was diminished only in the caudatus-putamen; treatment with 6-OHDA alone resulted in diminished fluorescence in the hypothalamus and in the intermediate but not the external layer of the median eminence. The neonatal administration of α-MPT had no significant effect on either the growth rate or the timing of puberty. Regular oestrous cycles occured after puberty in animals treated with either 6-OHDA or α-MPT.The PMSG-induced LH surge was significantly enhanced by 6-OHDA (administered i.v.) plus DMI, and reduced by 6-OHDA injected into the lateral ventricle (v). The inhibitory effect of 6-OHDA (v) wasreduced by DMI, but in animals given 6-OHDA (i.v.) after pargyline there was a marked reduction in the height of the LH surge. There was a good correlation between the changes in the concentrations of LH in peripheral plasma and the concentrations of GnRH in pituitary stalk plasma in that the PMSG-induced surge of GnRH was significantly increased by 6-OHDA (i.v.) plus DMI and reduced by 6-OHDA (v). In animals treated with 6-OHDA (i.v.) plus DMI catecholamine fluorescence was reduced only in the external layer of the median eminence, while after 6-OHDA (v) plus DMI degeneration was seen in the medial forebrain bundle.These results demonstrate a marked difference between the long-term and acute effects of 6-OHDA on the gonadotropin control system. Neonatal treatment with 6-OHDA plus DMI significantly delays puberty and the rate of body growth, but does not affect cyclical gonadotropin release and has no persistent effect on the hypothalamic catecholaminergic systems. The acute administration of 6-OHDA, depending upon the route of administration and whether it is given after DMI, can either potentiate or inhibit the PMSG-induced surge of GnRH and consequently LH by mechanisms which involve destruction, respectively, of either dopaminergic terminals in the median eminence or catecholaminergic fibres in the dorsal hypothalamus.     

Protective effect of quinacrine on striatal dopamine levels in 6-OHDA and MPTP models of Parkinsonism in rodents

Recent studies provide evidence that phospholipase A2 (PLA2) may play a role in the development of experimental parkinsonism. In this investigation an attempt was made to determine a possible protective effect of quinacrine (QNC), a PLA2 inhibitor on MPTP as well as 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in rodents. For MPTP studies, adult male mice (C57 BL) were treated with MPTP (30 mg/kg, i.p.) daily for 5 days. QNC was injected i.p. in the doses of 0, 10, 30 and 60 mg/kg daily 30 min before MPTP in four different groups. Two other groups of mice received either vehicle (control) or a high dose of QNC (60 mg/kg). Two hours after the last injection of MPTP, striata were collected for the analysis of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and glutathione (GSH). For the 6-OHDA study, male Wistar rats were infused with 6-OHDA (60 microg) in the right striatum under chloral hydrate anesthesia. The rats in different groups were treated with 0, 5, 15 and 30 mg/kg QNC (i.p.) for 4 days, while first injection was given 30 min before 6-OHDA. On day 5, rats were sacrificed and striata were stored at -80 degrees C. Administration of MPTP or 6-OHDA significantly reduced striatal DA, which was significantly attenuated by QNC. Concomitant treatment with QNC also protected animals against MPTP or 6-OHDA-induced depletion of striatal GSH. Our findings clearly suggest the role of PLA2 in MPTP and 6-OHDA induced neurotoxicity and oxidative stress. However, further studies are warranted to explore the therapeutic potential of PLA2 inhibitors for the treatment of Parkinson's disease.     

Depletion of brain glutathione potentiates the effect of 6-hydroxydopamine in a rat model of Parkinson’s disease

In order to examine the possible role of rat brain glutathione depletion by diethyl maleate (DEM) in the potentiation of 6-hydroxydopamine (6-OHDA) neurotoxicity, the relationships between both effects were evaluated using the circling behavior test (CBT), and determining striatal glutathione S-transferase (GST)-specific activity. There were significant differences between the two studied groups: 6-OHDA and DEM + 6-OHDA lesioned animals in striatal glutathione (GSH) concentration at the moment of the lesion with 6-OHDA and also at the end of the experiment (30 d after 6-OHDA lesion). The circling behavior test following the administration of amphetamine was qualitatively different between both groups of simple-and double-damaged animals. In accordance with our results, DEM injury makes the animals more susceptible to brain-oxidative damage by 6-OHDA, which can indicate that in the double-damaged animal group, DEM could induce potentiation of the toxicity through striatal glutathione depletion.     

黄芪甲苷对PC12细胞氧化应激损伤的保护作用

目的 探讨黄芪甲苷对PC12细胞氧化应激损伤的作用。方法 体外培养PC12细胞，6-羟基多巴胺（6-OHDA）作用PC12细胞导致氧化应激损伤。根据细胞作用方法随机分为4组:①对照组，采用完全培养基正常培养；②6-OHDA组，给予终浓度为100 μmol/L的6-OHDA处理24 h；③低、中、高剂量黄芪甲苷组，分别给予终浓度为25、50、100 μmol/L的黄芪甲苷预处理24 h，然后给予终浓度为100 μmol/L 6-OHDA处理24 h；④AG490组，以20 μmol/L AG490（JAK2/STAT3信号通路抑制剂）预处理16 h，加入终浓度为100 μmol/L黄芪甲苷处理24 h，然后再给予终浓度为100 μmol/L 6-OHDA处理24 h。CCK8法检测细胞生存率，流式细胞仪检测细胞凋亡率，酶联免疫吸附实验法检测细胞上清液超氧化物歧化酶（SOD）和丙二醛（MDA）水平，免疫印迹法检测细胞p-JAK2和p-STAT3蛋白表达。结果 6-OHDA作用后，PC12细胞存活率明显降低，细胞凋亡率明显升高，细胞培养液SOD水平明显降低、MDA水平明显升高，细胞p-JAK2和p-STAT3蛋白表达水平明显降低；黄芪甲苷预处理明显逆转6-OHDA的作用，而且呈剂量依赖性；AG490预处理明显逆转黄芪甲苷的作用。结论 6-OHDA作用PC12细胞，可导致氧化应激损伤促使细胞凋亡；黄芪甲苷预处理能激活JAK2/STAT3信号通路，抑制6-OHDA对PC12细胞的损伤，对PC12细胞起保护作用。     

Dopamine agonists and analogues have an antiproliferative effect on CHO-K1 cells

Epidemiological studies have shown a reduced incidence of cancer in Parkinson's disease. Since nearly all parkinsonian patients with clinical impairment are treated with L-beta-3,4-dihydroxyphenylalanine (L-DOPA) and dopamine (DA)ergic agonists, a possibility exists that these therapeutic agents can influence the risk of cancer. We studied the antiproliferative effect of these therapeutic agents (and substances structurally correlated) on Chinese hamster ovary (CHO)-K1 cell growth. Among the compounds tested, apomorphine proved to be the most potent inhibitor of CHO-K1 cell growth, with an EC(50) of 3.35 +/- 0.12 micro M. The apomorphine analogues, apocodeine and hydroxyethylnorapomorphine, were less active as inhibitors of CHO-K1 cell growth. The activity of DA, 6-hydroxydopamine (6-OHDA), phenylethylamine (PEA), L-DOPA and bromocriptine as antiproliferative was one order of magnitude lower than that of apomorphine while pergolide was ineffective. To test whether or not the oxidative potential of these compounds was important for their antiproliferative effect, several antioxidants were assayed. Among them glutathione (GSH) and dithiothreitol (DTT) were effective in reversing the anti-proliferative effect of apomorphine, DA, 6-OHDA and PEA, conversely they did not work with bromocriptine. GSH and DTT are sulphydryl-reducing agents; while their effect could explain the efficacy against apomorphine, DA and 6-OHDA, it is difficult to understand why they should have any effect on PEA as this substance does not react with sulphydryl groups. The oxidative potential as a mechanism of action was also questioned by the results obtained with dihydrorhodamine 123, a probe that changes its fluorescent emission wave when oxidized. None of the compounds, with the exception of 6-OHDA, had any effect on the fluorescent emission wave of the probe at the maximal concentrations used to inhibit CHO-K1 cell growth. At concentrations five times higher, apomorphine and DA generated reactive oxygen species but PEA and bromocriptine did not. These data demonstrate that the antiproliferative effect of these compounds is not due to their oxidative potential, but another mechanism must be postulated.     

Rutin Protects Dopaminergic Neurons from Oxidative Stress in an Animal Model of Parkinson’s Disease

This study was undertaken to investigate the neuroprotective effects of rutin (vitamin P) on 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD) in rats. Oxidative stress and inflammation is an important event, play a crucial role in neurodegenerative diseases. Rutin has been shown to have antioxidant and anti-inflammatory actions, and thus was tested for its beneficial effects using 6-OHDA-induced PD rat model. Male Wistar rats were pre-treated with rutin (25?mg/kg bwt, orally) for 3?weeks and subjected to unilateral intrastriatal injection of 6-OHDA (10?μg in 0.1% ascorbic acid in normal saline). Three weeks after 6-OHDA infusion, rats were tested for neurobehavioral activity, and were killed after 4?weeks of 6-OHDA infusion for the estimation of thiobarbituric acid reactive substances, glutathione, and its dependent enzymes (glutathione peroxidase and glutathione reductase), dopamine (DA) and its metabolite 3,4-dihydroxyphenyl acetic acid. The increase in 6-OHDA-induced rotations and deficits in locomotor activity and motor coordination and decrease in antioxidant level, DA content and its metabolite and increase in the number of dopaminergic D2 receptors in striatum were protected significantly with lesioned group pre-treated with rutin. These findings were further supported by the histopathological and immunohistochemical findings in the substantia nigra that showed that rutin protected neurons from deleterious effects of 6-OHDA. These results suggest that the consumption of rutin, which is novel vitamin, may have the possibility of protective effect against the neurological disorder such as PD.     

Alteration of seizures resulting from pinealectomy in the rat after neonatal treatment with 6-hydroxydopamine

Convulsions from combined pinealectomy and parathyroidectomy were examined in rats treated as neonates with 6-hydroxydopamine (6-OHDA). Injection of 6-OHDA caused a significant reduction in the average latency to onset of clonic-tonic convulsions. Moreover, of the 6-OHDA-treated rats which convulsed, nearly half of them died during a seizure. In sham-pinealectomized rats, neonatal treatment with 6-OHDA reduced norepinephrine (NE) and increased dopamine levels in the forebrain while brainstem levels of NE were increased. Pretreatment with desmethylimipramine reversed the effects of 6-OHDA on convulsions and catecholamine levels. The results indicate that catecholamine lesions with 6-OHDA exacerbate convulsions from pinealectomy.