The effects of docosahexaenoic acid on glial derived neurotrophic factor and neurturin in bilateral rat model of Parkinson's disease

Parkinson's disease (PD) is the second most common neurodegenerative disorder marked by cell death in the Substantia nigra (SN). Docosahexaenoic acid (DHA) is the major polyunsaturated fatty acid (PUFA) in the phospholipid fraction of the brain and is required for normal cellular function. Glial cell line derived neurotrophic factor (GDNF) and neurturin (NTN) are very potent trophic factors for PD. The aim of the study was to evaluate the neuroprotective effects of GDNF and NTN by investigating their immunostaining levels after administration of DHA in a model of PD. For this reason we hypothesized that DHA administration of PD might alter GDNF, NTN expression in SN. MPTP neurotoxin that induces dopaminergic neurodegeneration was used to create the experimental Parkinsonism model. Rats were divided into; control, DHA-treated (DHA), MPTP-induced (MPTP), MPTP-induced+DHA-treated (MPTP+DHA) groups. Dopaminergic neuron numbers were clearly decreased in MPTP, but showed an increase in MPTP+DHA group. As a result of this, DHA administration protected dopaminergic neurons as shown by tyrosine hydroxylase immunohistochemistry. In the MPTP+DHA group, GDNF, NTN immunoreactions in dopaminergic neurons were higher than that of the MPTP group. In conclusion, the characterization of GDNF and NTN will certainly help elucidate the mechanism of DHA action, and lead to better strategies for the use of DHA to treat neurodegenerative diseases.     

雌激素对6-羟基多巴胺损伤黑质多巴胺能神经元的保护作用

本研究以P50听觉诱发电位(P50 auditory evoked potential, P50)和酪氨酸羟化酶(tyrosine hydroxylase, TH)阳性细胞计数作为黑质功能和形态学指标,动态追踪研究雌激素对6-羟基多巴胺(6-hydroxydopamine, 6-OHDA)损伤黑质多巴胺(dopamine, DA)能神经元的作用.将大鼠分为4组:(1)正常雌性大鼠对照组;(2)单纯帕金森氏病(Parkinson's disease, PD)模型组;(3)双侧去卵巢PD模型组;(4)去卵巢回补3d雌激素的PD模型组.在大鼠清醒和安静的生理状态下连续14d记录黑质的P50,并检测黑质TH 细胞数目的变化.结果显示:单纯PD模型大鼠黑质P50的T/C值较正常雌鼠降低40.60%(P<0.01),其损伤侧黑质TH 细胞数目减少64.74%(P<0.01);去卵巢PD模型大鼠黑质P50的T/C值较单纯PD模型大鼠进一步降低45.88%(P<0.01),同时其黑质TH 细胞数目值也进一步减少57.26%(P<0.01),表明急性缺乏生理水平性腺雌激素将增大6-OHDA损伤黑质DA能神经元的程度,同时使黑质的感觉门控(sensory gating, SG)功能明显受损;去卵巢后回补3d生理剂量雌激素,可明显改善大鼠黑质的SG功能,提高TH 细胞数量(与去卵巢PD模型大鼠比较,P<0.01),其黑质损伤程度与单纯PD模型大鼠相当.以上结果提示,生理水平的雌激素具有提高黑质DA能神经元对伤害性刺激耐受性的神经保护作用.缺乏性腺源性的雌激素时,及时给予生理剂量的雌激素可以减轻神经毒素6-OHDA对黑质DA能神经元结构和功能的损伤.     

The influence and the mechanism of docosahexaenoic acid on a mouse model of Parkinson's disease

This study aimed to investigate the effects of docosahexaenoic acid (DHA) on the oxidative stress that occurs in an experimental mouse model of Parkinson’s disease (PD). An experimental model of PD was created by four intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (4 × 20 mg/kg, at 12 h intervals). Docosahexaenoic acid was given daily by gavage for 4 weeks (36 mg/kg/day). The motor activity of the mice was evaluated via the pole test, and the dopaminergic lesion was determined by immunohistochemical analysis for tyrosine hydroxylase (TH)-immunopositive cells. The activity of antioxidant enzymes in the brain were determined by spectrophotometric assays and the concentration of thiobarbituric acid-reactive substances (TBARS) were measured as an index of oxidative damage. The number of apoptotic dopaminergic cells significantly increased in MPTP-treated mice compared to controls. Although DHA significantly diminished the number of cell deaths in MPTP-treated mice, it did not improve the decreased motor activity observed in the experimental PD model. Docosahexaenoic acid significantly diminished the amount of cell death in the MPTP + DHA group as compared to the MPTP group. TBARS levels in the brain were significantly increased following MPTP treatment. Glutathione peroxidase (GPx) and catalase (CAT) activities of brain were unaltered in all groups. The activity of brain superoxide dismutase (SOD) was decreased in the MPTP-treated group compared to the control group, but DHA treatment did not have an effect on SOD activity in the MPTP + DHA group. Our current data show that DHA treatment exerts neuroprotective actions on an experimental mouse model of PD. There was a decrease tendency in brain lipid oxidation of MPTP mice but it did not significantly.     

Neuroprotective Effects of Tetramethylpyrazine against Dopaminergic Neuron Injury in a Rat Model of Parkinson's Disease Induced by MPTP

Parkinson''s disease (PD) is the second most prevalent progressive neurodegenerative disease. Although several hypotheses have been proposed to explain the pathogenesis of PD, apoptotic cell death and oxidative stress are the most prevalent mechanisms. Tetramethylpyrazine (TMP) is a biological component that has been extracted from Ligusticum wallichii Franchat (ChuanXiong), which exhibits anti-apoptotic and antioxidant roles. In the current study, we aimed to investigate the possible protective effect of TMP against dopaminergic neuron injury in a rat model of Parkinson''s disease induced by MPTP and to elucidate probable molecular mechanisms. The results showed that TMP could notably prevent MPTP-induced dopaminergic neurons damage, reflected by improvement of motor deficits, enhancement of TH expression and the content of dopamine and its metabolite, DOPAC. We observed MPTP-induced activation of mitochondrial apoptotic death pathway, evidenced by up-regulation of Bax, down-regulation of Bcl-2, release of cytochrome c and cleavage of caspase 3, which was significantly inhibited by TMP. Moreover, TMP could prevent MPTP-increased TBARS level and MPTP-decreased GSH level, indicating the antioxidant role of TMP in PD model. And the antioxidant role of TMP attributes to the prevention of MPTP-induced reduction of Nrf2 and GCLc expression. In conclusion, in MPTP-induced PD model, TMP prevents the down-regulation of Nrf2 and GCLc, maintaining redox balance and inhibiting apoptosis, leading to the attenuation of dopaminergic neuron damage. The effectiveness of TMP in treating PD potentially leads to interesting therapeutic perspectives.     

Recombinant human granulocyte colony-stimulating factor protects against MPTP-induced dopaminergic cell death in mice by altering Bcl-2/Bax expression levels

Granulocyte colony-stimulating factor (G-CSF) has been used for the treatment of neutropenia in hematologic disorders. The neuroprotective effects of G-CSF were reported in neurological disease models. In the present study, we examined whether G-CSF can protect dopaminergic neurons against MPTP-induced cell death in a mouse model of Parkinson's disease. Mice of one group were injected intraperitoneally with MPTP for five consecutive days, those of another group with MPTP and intraperitoneal G-CSF at 2 days and 1 day before the first MPTP injection, and 30 min before each MPTP injection, while control mice received saline injections. Immunohistochemistry, western blotting analysis, and HPLC were performed to evaluate damage of substantia nigra dopaminergic neurons and expression of Bcl-2 and Bax protein. MPTP induced dopaminergic cell death in the substantia nigra. G-CSF significantly prevented MPTP-induced loss of tyrosine hydroxylase-positive neurons (p < 0.05), increased Bcl-2 protein and decreased Bax protein expression. Our findings indicate that G-CSF provides neuroprotection against MPTP-induced cell death and this effect is mediated by increasing Bcl-2 expression levels and decreasing Bax expression levels in C57BL/6 mice.     

Tauroursodeoxycholic Acid Prevents MPTP-Induced Dopaminergic Cell Death in a Mouse Model of Parkinson’s Disease

Mitochondrial dysfunction and oxidative stress are implicated in the neurodegenerative process in Parkinson??s disease (PD). Moreover, c-Jun N-terminal kinase (JNK) plays an important role in dopaminergic neuronal death in substantia nigra pars compacta. Tauroursodeoxycholic acid (TUDCA) acts as a mitochondrial stabilizer and anti-apoptotic agent in several models of neurodegenerative diseases. Here, we investigated the role of TUDCA in preventing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration in a mouse model of PD. We evaluated whether TUDCA modulates MPTP-induced degeneration of dopaminergic neurons in the nigrostriatal axis, and if that can be explained by regulation of JNK phosphorylation, reactive oxygen species (ROS) production, glutathione S-transferase (GST) catalytic activation, and Akt signaling, using C57BL/6 glutathione S-transferase pi (GSTP) null mice. TUDCA efficiently protected against MPTP-induced dopaminergic degeneration. We have previously demonstrated that exacerbated JNK activation in GSTP null mice resulted in increased susceptibility to MPTP neurotoxicity. Interestingly, pre-treatment with TUDCA prevented MPTP-induced JNK phosphorylation in mouse midbrain and striatum. Moreover, the anti-oxidative role of TUDCA was demonstrated in vivo by impairment of ROS production in the presence of MPTP. Finally, results herein suggest that the survival pathway activated by TUDCA involves Akt signaling, including downstream Bad phosphorylation and NF-??B activation. We conclude that TUDCA is neuroprotective in an in vivo model of PD, acting mainly by modulation of JNK activity and cellular redox thresholds, together with activation of the Akt pro-survival pathway. These results open new perspectives for the pharmacological use of TUDCA, as a modulator of neurodegeneration in PD.     

Angiogenin in Parkinson Disease Models: Role of Akt Phosphorylation and Evaluation of AAV-Mediated Angiogenin Expression in MPTP Treated Mice

The angiogenic factor, angiogenin, has been recently linked to both Amyotrophic Lateral Sclerosis (ALS) and Parkinson Disease (PD). We have recently shown that endogenous angiogenin levels are dramatically reduced in an alpha-synuclein mouse model of PD and that exogenous angiogenin protects against cell loss in neurotoxin-based cellular models of PD. Here, we extend our studies to examine whether activation of the prosurvival Akt pathway is required for angiogenin''s neuroprotective effects against 1-methyl-4-phenylpyridinium (MPP+), as observed in ALS models, and to test the effect of virally-mediated overexpression of angiogenin in an in vivo PD model. Using a dominant negative Akt construct, we demonstrate that inhibition of the Akt pathway does not reduce the protective effect of angiogenin against MPP+ toxicity in the dopaminergic SH-SY5Y cell line. Furthermore, an ALS-associated mutant of angiogenin, K40I, which fails to induce Akt phosphorylation, was similar to wildtype angiogenin in protection against MPP+. These results confirm previous work showing neuroprotective effects of angiogenin against MPP+, and indicate that Akt is not required for this protective effect. We also investigated whether adeno-associated viral serotype 2 (AAV2)-mediated overexpression of angiogenin protects against dopaminergic neuron loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model. We found that angiogenin overexpression using this approach does not reduce the MPTP-induced degeneration of dopaminergic cells in the substantia nigra, nor limit the depletion of dopamine and its metabolites in the striatum. Together, these findings extend the evidence for protective effects of angiogenin in vitro, but also suggest that further study of in vivo models is required to translate these effects into meaningful therapies.     

Protective effects of PEP-1-Catalase on stress-induced cellular toxicity and MPTP-induced Parkinson’s disease

Parkinson’s disease (PD) is a neurodegenerative disability caused by a decrease of dopaminergic neurons in the substantia nigra (SN). Although the etiology of PD is not clear, oxidative stress is believed to lead to PD. Catalase is antioxidant enzyme which plays an active role in cells as a reactive oxygen species (ROS) scavenger. Thus, we investigated whether PEP-1-Catalase protects against 1-methyl-4-phenylpyridinium (MPP⁺) induced SH-SY5Y neuronal cell death and in a 1-methyl-4-phenyl-1,2,3,6-trtrahydropyridine (MPTP) induced PD animal model. PEP-1-Catalase transduced into SH-SY5Y cells significantly protecting them against MPP⁺-induced death by decreasing ROS and regulating cellular survival signals including Akt, Bax, Bcl-2, and p38. Immunohistochemical analysis showed that transduced PEP-1-Catalase markedly protected against neuronal cell death in the SN in the PD animal model. Our results indicate that PEP-1-Catalase may have potential as a therapeutic agent for PD and other oxidative stress related diseases. [BMB Reports 2015; 48(7): 395-400]     

Rifampicin Prevents SH-SY5Y Cells from Rotenone-Induced Apoptosis via the PI3K/Akt/GSK-3β/CREB Signaling Pathway

In addition to its original application for treating tuberculosis, rifampicin has multiple potential neuroprotective effects in chronic neurodegenerative diseases including Parkinson’s disease (PD) and Alzheimer’s disease. Inflammatory reactions and the PI3K/Akt pathway are strongly implicated in dopaminergic neuronal death in PD. This study aims to investigate whether rifampicin protects rotenone-lesioned SH-SY5Y cells via regulating PI3K/Akt/GSK-3β/CREB pathway. Rotenone-treated SH-SY5Y cells were used as the cell model to investigate the neuroprotective effects of rifampicin. Cell viability and apoptosis of SH-SY5Y cells were determined by CCK-8 assay and flow cytometry, respectively. The expression of Akt, p-Akt, GSK-3β, p-GSK-3β, CREB and p-CREB were measured by Western blot. Our results showed that the cell viability and level of phospho-CREB significantly decreased in SH-SY5Y cells exposed to rotenone when compared to the control group. Both the cell viability and the expression of phospho-CREB in cells pretreated with rifampicin were higher than those of cells exposed to rotenone alone. Moreover, pretreatment of SH-SY5Y cells with rifampicin enhanced phosphorylation of Akt and suppressed activity of GSK-3β. The addition of LY294002, a PI3K inhibitor, could suppress phosphorylation of Akt and CREB and activate GSK-3β, resulting in abolishment of neuroprotective effects of rifampicin on cells exposed to rotenone. Rifampicin provides neuroprotection against dopaminergic degeneration, partially via the PI3K/Akt/GSK-3β/CREB signaling pathway. These findings suggest that rifampicin could be an effective and promising neuroprotective candidate for treating PD.     

软脂酸对胰岛β细胞凋亡及Akt途径的影响

目的：探讨软脂酸（PA）对胰岛β细胞（MIN6细胞）凋亡及Akt信号途径的影响。方法：细胞采用小鼠胰岛素瘤细胞株MIN6,不同浓度PA（0-1．6mmol／L）干预24、48h,MTT、法测定各组细胞存活率。干预48h后Hoechst-PI染色法和Annexin—V／PI双标流式测定法测定各组细胞凋亡率,Western-blot法测定p-Akt、Akt、Bax、Bcl-2。结果：随着PA浓度的增高①MIN6细胞存活率逐渐减小、凋亡率逐渐增大;②MIN6细胞中p-Akt和Bcl-2的表达逐渐减少,而Akt、Bax无明显改变。结论：长时间PA作用引起MIN6细胞凋亡,并呈现一定的量效关系;这一效应可能是通过Akt／Bcl-2产生作用的。     

Differential expression of Bcl-2 and APP immunoreactivity after intrastriatal injection of MPP+ in the rat.

While there is growing evidence that Bcl-2 proto-oncogene and beta-amyloid precursor proteins (APP) are neuroprotective in function, our recent studies have demonstrated that Bcl-2 and APP may be co-expressed and co-regulated in retinal neurons or glia under normal or experimental conditions. Whether Bcl-2 and APP are functionally coupled in other neuronal systems is not clear. This issue was investigated further in the present experiments by examining the expression pattern of two molecules after unilateral intrastriatal injection of 1-methyl-4-phenyl-pyridinium (MPP(+)), a neurotoxic metabolite that selectively damages dopaminergic neurons. One hour to 2 months after MPP(+) injection into rat striatum, a significant increase in Bcl-2 expression was observed in distinct populations of neurons, astrocyte-like and OX-42-positive cells not only in traumatic regions but also in remote areas including the ipsilateral cortex and substantia nigra (SN). No detectable change was observed in the striatum, cortex or SN on the contralateral side of the brain. The immunoreactive pattern and time-dependent APP increase was similar to that of Bcl-2 in the severely injured striatum and cortex. However, an up-regulation of Bcl-2 expression, but not APP, appears in dopaminergic neurons in the ipsilateral SN pars compacta where there was retrograde degeneration. In contrast, APP immunoreactivity was decreased in the hippocampus following intrastriatal injury, whereas, no alteration in Bcl-2 expression was detected. The differential changes in Bcl-2 and APP expression in nigral neurons and some other brain tissues suggest that these proteins may not be co-regulated by a common mechanism, at least in certain neuronal pathways.     

鞘内注射Akt特异性抑制剂GSK690693抑制骨癌诱导的大鼠痛相关行为的研究

目的:探讨在大鼠乳腺癌骨转移诱导癌症疼痛的调控过程中Akt信号通路的作用。方法:将Wistar成模wistar大鼠随机分为Model组、Model+GSK690693组及Model+Saline组;Model组大鼠不进行鞘内注射,Model+GSK690693组及Model+Saline组大鼠,于手术后数天(post-cancer cell implantation day,PID)PID 13 d、14 d及21 d鞘内分别注入Akt特异抑制剂GSK690693、等量生理盐水组,分别于PID 0 d、7 d、14 d及21 d,观察大鼠痛相关行为学检查,PID 21 d取DRG行免疫印迹检查p-Akt表达。结果:在鞘内注射Akt特异性抑制剂GSK690693后,Model+GSK690693组大鼠的机械缩足反射阈值上升,自发性疼痛行为值及患侧DRG中p-Akt表达下降。在PID 14 d、21 d等不同时间节点,Model+GSK690693组大鼠的疼痛行为学与Model+Saline组大鼠、Model组大鼠经统计学比较有显著的统计学差异(P0.01);PID 21d Model+GSK690693组大鼠患侧DRG中p-Akt表达与Model组的比较有显著统计学意义(P0.01),与Model+Saline组比较有统计学意义(P0.05);结论:鞘内注射Akt特异性抑制剂GSK690693可抑制大鼠乳腺癌骨转移诱导的大鼠痛相关行为。     

PEP-1–ribosomal protein S3 protects dopaminergic neurons in an MPTP-induced Parkinson's disease mouse model

Parkinson's disease (PD) is a neurodegenerative disease characterized by a gradual loss of dopaminergic (DA) neurons in the substantia nigra (SN) of the brain. Ribosomal protein S3 (rpS3) has multiple functions related to protein synthesis, antioxidative activity, and UV endonuclease III activity. We have previously shown that PEP-1–rpS3 inhibits skin inflammation and provides neuroprotection against experimental cerebral ischemic damage. In this study, we examined whether PEP-1–rpS3 can protect DA neurons against oxidative stress in SH-SY5Y neuroblastoma cells and in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. PEP-1–rpS3 was efficiently delivered to SH-SY5Y cells and the SN of the brain as confirmed by Western blot and immunohistochemical analysis. PEP-1–rpS3 significantly inhibited reactive oxygen species generation and DNA fragmentation induced by 1-methyl-4-phenylpyridinium, consequently leading to the survival of SH-SY5Y cells. The neuroprotection was related to the antiapoptotic activity of PEP-1–rpS3 that affected the levels of proapoptotic and antiapoptotic mediators. In addition, immunohistochemical data collected using a tyrosine hydroxylase antibody and cresyl violet staining demonstrated that PEP-1–rpS3 markedly protected DA cells in the SN against MPTP-induced oxidative stress. Therefore, our results suggest that PEP-1–rpS3 may be a potential therapy for PD.     

小剂量多虑平对大鼠应激性胃黏膜损伤的治疗作用

目的:探讨小剂量多虑平(Doxepin)对大鼠应激性胃黏膜损伤(stress gastric mucosal damage,SGMD)的治疗作用,并就其可能机制初步研究.方法:采用浸水加束缚的方法制备大鼠应激性胃黏膜损伤模型.健康雄性SD大鼠50只,随机分为5组:假手术组(Sham组)、应激性胃黏膜损伤组(SGMD组)...     

Cardiotrophin-1 stimulates the neural differentiation of human umbilical cord blood-derived mesenchymal stem cells and survival of differentiated cells through PI3K/Akt-dependent signaling pathways

Cardiotrophin-1 (CT1) plays an important role in the differentiation, development, and survival of neural stem cells. In this study, we analyzed its effects on the stimulation of human umbilical cord blood-derived mesenchymal stem cells in terms of their potential to differentiate into neuron-like cells, their survival characteristics, and the molecular mechanisms involved. The treatment of cells with neural induction medium (NIM) and CT1 generated more cells that were neuron-like and produced stronger expression of neural-lineage markers than cells treated with NIM and without CT1. Bcl-2 and Akt phosphorylation (p-Akt) expression levels increased significantly in cells treated with both NIM and CT1. This treatment also effectively blocked cell death following neural induction and decreased Bax, Bak and cleaved-caspase 3 expression compared with cells treated with NIM without CT1. In addition, the inhibition of phosphatidylinositol 3-kinase (PI3K) abrogated p-Akt and Bcl-2 expression. Thus, PI3K/Akt contribute to CT1-stimulated neural differentiation and to the survival of differentiated cells.     

双氢青蒿素对Raji细胞放射敏感性的影响

目的：研究双氢青蒿素（DHA）对Raji细胞放射敏感性的影响并探讨其作用机制。方法：CCK8测定DHA对Raji细胞活力的影响,流式细胞术检测细胞凋亡、胞内ROS及线粒体膜电位,Western blot检测AKT、p-AKT、Bcl-2、Bax和Cleaved-Caspase-3蛋白表达量。结果：实验分为对照组、DHA组（5 μmol/L DHA）、放射组（4 Gy γ射线）、联合放射组（5 μmol/L DHA和4 Gy γ射线）,与其他3组相比,联合放射组Raji细胞的线粒体膜电位显著降低（P<0.01）,胞内ROS含量和凋亡率显著升高（P<0.01）;此外,Raji细胞AKT表达量与其他3组相比无明显差异,但AKT的磷酸化受到抑制;Bcl-2表达量显著降低,而Bax、Cleaved-Caspase-3表达量显著升高。结论：DHA可能通过抑制磷酸肌醇3-激酶（PI3K-AKT）信号通路及激活了Raji细胞的线粒体凋亡途径,引起氧化应激反应,从而增加Raji细胞对放射的敏感性。     

Ubiquitin–Proteasome System Impairment and MPTP-Induced Oxidative Stress in the Brain of C57BL/6 Wild-type and GSTP Knockout Mice

The ubiquitin–proteasome system (UPS) is the primary proteolytic complex responsible for the elimination of damaged and misfolded intracellular proteins, often formed upon oxidative stress. Parkinson’s disease (PD) is neuropathologically characterized by selective death of dopaminergic neurons in the substantia nigra (SN) and accumulation of intracytoplasmic inclusions of aggregated proteins. Along with mitochondrial dysfunction and oxidative stress, defects in the UPS have been implicated in PD. Glutathione S-transferase pi (GSTP) is a phase II detoxifying enzyme displaying important defensive roles against the accumulation of reactive metabolites that potentiate the aggression of SN neuronal cells, by regulating several processes including S-glutathionylation, modulation of glutathione levels and control of kinase-catalytic activities. In this work we used C57BL/6 wild-type and GSTP knockout mice to elucidate the effect of both MPTP and MG132 in the UPS function and to clarify if the absence of GSTP alters the response of this pathway to the neurotoxin and proteasome inhibitor insults. Our results demonstrate that different components of the UPS have different susceptibilities to oxidative stress. Importantly, when compared to the wild-type, GSTP knockout mice display decreased ubiquitination capacity and overall increased susceptibility to UPS damage and inactivation upon MPTP-induced oxidative stress.     

神经节苷脂GM1对帕金森模型小鼠黑质细胞凋亡及Bcl-2和Bax表达的影响

目的观察神经节苷脂GM1对帕金森模型小鼠黑质细胞凋亡及Bcl-2和Bax表达的影响,探讨其预防帕金森病的机制。方法成年C57-BL雄性小鼠分为正常对照组、模型组和神经节苷脂GMI治疗组。应用TUNEL法和免疫荧光组织化学染色技术观察各组小鼠黑质神经元凋亡及Bcl-2和Bax表达情况。结果TUNEL、Bcl-2和Bax阳性神经元主要位于黑质致密部。模型组黑质神经元凋亡数明显多于正常对照组,神经节苷脂GM1组黑质神经元凋亡数明显少于模型组。在模型组Bcl-2阳性神经元和Bax阳性神经元的数量均较正常对照组明显增多;在神经节苷脂GM1组Bcl-2阳性神经元的数量较模型组明显增多,但Bax阳性神经元的数量较模型组明显减少。结论神经节苷脂GM1可能通过增强黑质神经元内Bcl-2基因表达及抑制Bax基因表达的途径抑制黑质神经元的凋亡。     

Acupuncture enhances the synaptic dopamine availability to improve motor function in a mouse model of Parkinson's disease

Parkinson's disease (PD) is caused by the selective loss of dopaminergic neurons in the substantia nigra (SN) and the depletion of striatal dopamine (DA). Acupuncture, as an alternative therapy for PD, has beneficial effects in both PD patients and PD animal models, although the underlying mechanisms therein remain uncertain. The present study investigated whether acupuncture treatment affected dopamine neurotransmission in a PD mouse model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We found that acupuncture treatment at acupoint GB34 improved motor function with accompanying dopaminergic neuron protection against MPTP but did not restore striatal dopamine depletion. Instead, acupuncture treatment increased dopamine release that in turn, may lead to the enhancement of dopamine availability in the synaptic cleft. Moreover, acupuncture treatment mitigated MPTP-induced abnormal postsynaptic changes, suggesting that acupuncture treatment may increase postsynaptic dopamine neurotransmission and facilitate the normalization of basal ganglia activity. These results suggest that the acupuncture-induced enhancement of synaptic dopamine availability may play a critical role in motor function improvement against MPTP.