MPTP对小鼠不同脑区神经递质代谢酶基因表达的影响

1-甲基 -4 -苯基 -1,2 ,3 ,6-四氢吡啶 (MPTP)能够诱发黑质纹状体系统多巴胺能神经元损伤并产生与帕金森病类似的症状。本实验通过 MPTP注射诱导 C5 7BL小鼠神经元损伤 ,利用逆转录 PCR方法检测酪氨酸羟化酶 (TH)、单胺氧化酶 B(MAO-B)以及胆碱乙酰基转移酶 (Ch AT)三种神经递质代谢相关基因的表达变化。结果发现 ,在小鼠黑质与纹状体中 ,MPTP导致 TH基因表达显著降低 ,而 MAO-B与 Ch AT基因的表达变化在黑质与纹状体则有所不同 ,在黑质 MPTP导致 MAO-B与 Ch AT基因表达的上升 ,在纹状体则略有下降。     

Age-related severity of dopaminergic neurodegeneration to MPTP neurotoxicity causes motor dysfunction in C57BL/6 mice

This study investigated the influence of advancing age on dopaminergic neuronal degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication from the perspective concerning the relationship between dopaminergic function and behavioral features. Young (10 weeks) and older (14-15 months) C57BL/6 mice were treated with one to four injections of MPTP (20 mg/kg at 2h intervals). Although young mice showed no mortality in either MPTP treatment, older mice exhibited mortality from only two injections of MPTP during the experimental period. An extensive dopaminergic cell loss was found in both the striatum and substantia nigra of older mice given one and two injections of MPTP with marked decrease in striatal dopamine (DA) levels, but not young mice. We also found a behavioral change in the tail suspension test associated with the extent of decrease in striatal DA levels in MPTP-treated older mice, but not in young mice. These results clearly present age-related vulnerability to MPTP neurotoxicity in C57BL/6 mice and strongly support our previous report showing that there is a critical threshold level of the decrement in striatal DA contents causing motor dysfunction in this mouse model of Parkinson's disease.     

Effect of dopaminergic substances on sleep/wakefulness in saline- and MPTP-treated mice

Sleep/wakefulness (S/W) disorders are frequent in Parkinson's disease (PD). The underlying causes have yet to be elucidated but dopaminergic neurodegenerative lesions seem to contribute to appearance of the disorders and anti-Parkinsonian medication is known to accentuate S/W problems. Hence, we reasoned that studying the acute effect of dopaminergic compounds on S/W in an animal model of PD might improve our knowledge of S/W regulation in the context of partial dopaminergic depletion. To this end, we tested the effect of levodopa (l-dopa), pergolide (a mixed D(2)/D(1) agonist) and lisuride (a D(2) agonist) on S/W recordings in MPTP-treated mice, in comparison with controls. Our results showed that dopaminergic compounds modify S/W amounts in both control and MPTP mice. Wakefulness amounts are greater in MPTP mice after l-dopa (50 mg kg(-1)) and lisuride (1 mg kg(-1)) injections compared with control mice. Moreover, the paradoxical sleep latency was significantly longer in MPTP mice after high-dose l-dopa administration. Our observations suggest that the actions of both l-dopa and lisuride on S/W differ slightly in MPTP mice relative to controls. Hence, MPTP-induced partial DA depletion may modulate the effect of dopaminergic compounds on S/W regulation.     

Neuroprotective effect of baicalein against MPTP neurotoxicity: behavioral, biochemical and immunohistochemical profile

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes the damage of dopaminergic neurons as seen in Parkinson's disease (PD). Oxidative stress has been implicated in the pathogenesis of PD. Baicalein, isolated from the traditional Chinese herbal medicine Huangqin (Scutellaria baicalensis Georgi), has been shown to have antioxidant effects. Here we investigated the effect of baicalein on MPTP-induced neurotoxicity in mice. Pretreatment with baicalein for a week was followed by challenge with MPTP for 4 consecutive days; the subsequent behavioral, biochemical and immunohistochemical manifestations in mice were determined and compared to those in untreated mice and mice challenged only with MPTP. The present study showed that baicalein could improve the abnormal behavior in MPTP-treated mice. The protective effect may be caused by increasing the levels of DA and 5-HT in the striatum, increasing the counts of dopaminergic neurons, inhibiting oxidative stress and the astroglia response. These results suggest that baicalein possesses potent neuroprotective activity and may be a potential anti-Parkinson's disease drug that is worthy of further study.     

单唾液酸神经节苷脂(GM_1)对经MPTP破坏的小鼠黑质纹状体多巴胺神经元的保护作用

将1一甲基一4苯基一1.2.3.6四氢吡啶(MPTP)经腹腔注入小鼠,连续注射6天,一组动物注射后次日处死;另一组动物存活二周后处死;第三组动物在给予1—甲基一4苯基一1.2.3.6四氢吡啶的同时,经腹膜腔注射神经节苷脂持续三周;第四组为对照组.各组动物脑用酪氨酸羟化酶抗体进行免疫组化观察.结果发现1一甲基一4苯基一1.2.3.6四氢吡啶连续注射后次日处死的动物黑质致密部酪氨酸羟化酶阳性神经元数量明显减少,纹状体中酪氨酸羟化酶阳性终末亦明显稀疏.损害后存活二周组,不论黑质或纹状体的损害均略轻.单唾液酸神经节苷脂组黑质致密部酪氨酸羟化酶阳性神经元及纹状体中酪氨酸羟化酶阳性终末均较上两组明显增多.实验表明,单唾液酸神经节苷脂对经1一甲基一4苯基一1.2.3.6四氢吡啶破坏后的小鼠黑质纹状体系多巴胺神经元有保护作用,防止多巴胺神经元因损害引起的继发性退变.     

Altered CNS response to injury in the MRL/MpJ mouse

The MRL/MpJ mouse has a greatly enhanced healing response and an absence of scarring compared with other mouse strains. Following lesions to the CNS mammals show a scarring response known as reactive gliosis, and this CNS scar tissue blocks regeneration of cut axons. We have therefore compared reactive gliosis in the MRL/MpJ mouse and the Swiss Webster mouse, which exhibits normal scarring in the periphery. The lesion model was a stab lesion to the cortex, in which reactive gliosis has previously been quantified. Axon regeneration was examined following a cut lesion to the dopaminergic projection from the substantia nigra to the striatum used in previous regeneration experiments. In the MRL/MpJ following the lesion compared with Swiss Webster mice there was greater cell loss around the lesion followed by greater and more widespread and more prolonged cellular proliferation. Early after the lesion there was a greater loss of glial fibrillary acidic protein (GFAP)-positive astrocytes around the injury site in the MRL/MpJ, and an enhancement and prolongation of the microglial inflammatory response. This was accompanied by greater and more widespread blood-brain barrier leakage following injury. RNA levels for the matrix metalloproteinases (MMP)-2 and MMP-9 as well as for the thrombin receptors PAR-1 and PAR-4 were also greater at the MRL/MpJ injury site. All of these differences were transient and by 14 days post-injury there were no differences observed between MRL/MpJ and control mice. No axonal regeneration was observed following axotomy to the nigrostriatal pathway of the MRL/MpJ or the Swiss Webster mice at any time point.     

Neuroprotective effects of rotigotine in the acute MPTP-lesioned mouse model of Parkinson's disease

Dopamine agonists used to manage Parkinsonian motor symptoms have been suggested to be neuroprotective. The study was designed to assess the neuroprotective potential of the D(3)/D(2)/D(1) dopamine receptor agonist rotigotine in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned (MPTP) mouse model of Parkinson's disease by measuring mesencephalic degenerating neurons using FluoroJade staining and the remaining dopaminergic nerve endings in the striatum using dopamine transporter binding. Continuous administration of rotigotine at a dose of 3mg/kg significantly attenuated MPTP-induced acute cell degeneration in the FluoroJade-staining paradigm. Rotigotine (0.3-3mg/kg) partially protected dopamine nerve endings from MPTP-induced degeneration in a dose-dependent manner. These data suggest that rotigotine, at the doses employed, significantly protected dopamine neurons from degeneration in an acute mouse model of MPTP intoxication.     

帕金森病小鼠模型黑质纹状体通路的形态学改变

目的 观察帕金森病小鼠模型黑质纹状体通路随病程进展而发生的形态学变化,从新的视角探讨帕金森病的病理生理机制。方法 正常C57小鼠36只,随机分为生理盐水组和1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）组,每组18只,于注射后第7、14、21、25、28、35天取材,利用免疫组织化学、免疫荧光技术和激光扫描共焦显微镜观察黑质多巴胺能神经元的数量、在纹状体内投射的神经纤维密度及其在纹状体直接通路和间接通路神经元（D1R/D2R阳性神经元）上的分布比例。结果 注射MPTP后,黑质多巴胺能神经元减少40%～50%;纹状体内多巴胺能神经纤维数量呈现先减少后增加的过程：第21天最少,仅为正常的20%;第35天最高,达到正常的45%;多巴胺能神经纤维在纹状体D1R/D2R阳性神经元上的分布比例也有先低后高的表现：第21天最低,第35天最高,与生理盐水组相比差异有显著性。结论 MPTP帕金森病模型小鼠的黑质纹状体通路呈现多巴胺能神经纤维再生现象,再生的多巴胺能神经纤维更多地分布于其直接通路的神经元上。     

Role of alpha-synuclein in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice

In humans, mutations in the alpha-synuclein gene or exposure to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produce Parkinson's disease with loss of dopaminergic neurons and depletion of nigrostriatal dopamine. alpha-Synuclein is a vertebrate-specific component of presynaptic nerve terminals that may function in modulating synaptic transmission. To test whether MPTP toxicity involves alpha-synuclein, we generated alpha-synuclein-deficient mice by homologous recombination, and analyzed the effect of deleting alpha-synuclein on MPTP toxicity using these knockout mice. In addition, we examined commercially available mice that contain a spontaneous loss of the alpha-synuclein gene. As described previously, deletion of alpha-synuclein had no significant effects on brain structure or composition. In particular, the levels of synaptic proteins were not altered, and the concentrations of dopamine, dopamine metabolites, and dopaminergic proteins were unchanged. Upon acute MPTP challenge, alpha-synuclein knockout mice were partly protected from chronic depletion of nigrostriatal dopamine when compared with littermates of the same genetic background, whereas mice carrying the spontaneous deletion of the alpha-synuclein gene exhibited no protection. Furthermore, alpha-synuclein knockout mice but not the mice with the alpha-synuclein gene deletion were slightly more sensitive to methamphetamine than littermate control mice. These results demonstrate that alpha-synuclein is not obligatorily coupled to MPTP sensitivity, but can influence MPTP toxicity on some genetic backgrounds, and illustrate the need for extensive controls in studies aimed at describing the effects of mouse knockouts on MPTP sensitivity.     

Differential nicotinic receptor expression in monkey basal ganglia: effects of nigrostriatal damage

Our previous work showed that there were marked declines in (125)I-alpha-conotoxin MII labeled nicotinic receptors in monkey basal ganglia after nigrostriatal damage, findings that suggest alpha3/alpha6 containing nicotinic receptors sites may be of relevance to Parkinson's disease. We now investigate whether there are differential changes in the distribution pattern of nicotinic receptor subtypes in the basal ganglia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned animals compared to controls to better understand the changes occurring with nigrostriatal damage. To approach this we used (125)I-alpha-conotoxin MII, a marker for alpha3/alpha6 nicotinic receptors, and (125)I-epibatidine, a ligand that labels multiple nicotinic subtypes.The results demonstrate that there were medial to lateral gradients in nicotinic receptor distribution in control striatum, as well as ventromedial to dorsolateral gradients in the substantia nigra, which resembled those of the dopamine transporter in these same brain regions. Treatment with MPTP, a neurotoxin that selectively destroys dopaminergic nigrostriatal neurons, led to a relatively uniform decrease in nicotinic receptor sites in the striatum, but a differential effect in the substantia nigra with significantly greater declines in the ventrolateral portion. Competition analysis in the striatum showed that alpha-conotoxin MII sensitive sites were primarily affected after lesioning, whereas multiple nicotinic receptor populations were decreased in the substantia nigra.From these data we suggest that in the striatum alpha3/alpha6 nicotinic receptors are primarily localized on dopaminergic nerve terminals, while multiple nicotinic receptor subtypes are present on dopaminergic cell bodies in the substantia nigra. Thus, if activation of striatal nicotinic receptors is key in the regulation of basal ganglia function, alpha3/alpha6-directed nicotinic receptor ligands may be more relevant for Parkinson's disease therapy. However, nicotinic receptor ligands with a broader specificity may be more important if receptors in the substantia nigra play a dominant role in controlling nigrostriatal activity.     

Cyclooxygenase-2-deficient mice are resistant to 1-methyl-4-phenyl1, 2, 3, 6-tetrahydropyridine-induced damage of dopaminergic neurons in the substantia nigra

Cyclooxygenases (COX), key enzymes in prostanoid biosynthesis, may represent important therapeutic targets in various neurodegenerative diseases. In the present study, we explored the role of COX in Parkinson's disease (PD) by using 1-methyl-4-phenyl1, 2, 3, 6-tetrahydropyridine (MPTP) as a tool to create a rodent Parkinsonian model. MPTP (20 mg/kg, subcutaneously) was injected daily into COX-1- and COX-2-deficient mice and wild-type (WT) controls for five consecutive days. Immunocytochemical analysis of tissues collected 7 days after the final MPTP treatment showed that MPTP significantly decreased the number of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNc) of WT (40% decrease) and COX-1(-/-) (45% decrease) mutants. However, a much smaller loss of TH-ir neurons in COX-2(-/-) mutants (20% decrease) was observed. Furthermore, electrochemical analysis revealed a more than 70% decrease in the levels of dopamine and its metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid) in the striatum of the WT control COX-1(-/-) and COX-2(-/-) mutant mice. These results indicate that loss of COX-2 activity reduces MPTP-induced damage to the dopaminergic neurons of the SNc, but does not alter the levels of dopamine and its metabolites in the striatum. Interestingly, MPTP caused the same degree of loss of dopaminergic neurons in both COX-2(+/-) and COX-2(-/-) mice (20% loss). The results of this study indicate an important role of COX-2 in MPTP-induced neuronal degeneration and suggest the possibility that manipulation of the COX-2 could be an important target for therapeutic interventions in PD.     

MPTP对小鼠黑质与纹状体KIF基因表达的影响

目的: 揭示1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)对C57BL小鼠黑质与纹状体神经元驱动蛋白超家族(KIF)基因表达的影响。方法: 腹腔注射MPTP建立小鼠帕金森病动物模型,通过RT-PCR方法检测KIF1A、KIF2、KIF3A、KIF4与KIF5A基因的表达。结果: 在黑质中,MPTP造成KIF基因表达的普遍下降,只有KIF2基因表达无明显变化。在纹状体中则有所不同,KIF1A、KIF3A与KIF4基因表达上升,而KIF2与KIF5A表达的变化与在黑质中相似。结论: MPTP造成的神经黑质多巴胺能神经元丧失很可能与KIF基因表达的降低有关。     

Selective recovery of striatal 125I-alpha-conotoxinmii nicotinic receptors after nigrostriatal damage in monkeys

Evidence suggests that nicotinic receptors play a role in nigrostriatal function, a finding that may be relevant to Parkinson's disease. Knowledge of the conditions that regulate nicotinic receptor expression is therefore important. Previous studies showed that several different nicotinic receptors, including alpha-conotoxinMII (alpha-CtxMII)-sensitive receptors, are decreased after nigrostriatal damage. Nigrostriatal dopaminergic terminals also demonstrate a capacity for recovery after lesioning. The present experiments were therefore done to determine whether there were changes in striatal nicotinic receptors with recovery. To address this, we used two well-characterized animal models of nigrostriatal damage produced using the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Studies in mice showed that striatal 125I-alpha-CtxMII, as well as 125I-epibatidine and 125I-A85380 binding sites significantly recovered 1 month after lesioning, suggesting that alpha6* and most likely alpha4* receptors are increased. Experiments were next done in monkeys since striatal 125I-alpha-CtxMII receptors constitute a large percentage of nicotinic receptors and are more vulnerable to nigrostriatal damage in this model that closely mirrors Parkinson's disease. In monkeys allowed to recover from the toxic effects of MPTP for a 1-2 year period, there was a significant improvement in the Parkinson disability score. There was also a reversal in lesion-induced declines in striatal alpha-CtxMII-sensitive receptors, but no significant change in 125I-epibatidine and 125I-A85380 receptors. These findings suggest that alpha3*/alpha6* sites are selectively increased in monkey striatum with recovery. The present data show that recovery of 125I-alpha-CtxMII receptors occurs in parallel with the dopamine transporter, indicating that these nicotinic receptors sites are localized to presynaptic dopamine terminals in both species.     

MPTP treatment in mice does not transmit and cause Parkinsonian neurotoxicity in non-treated cagemates through close contact

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is currently a leading neurotoxic agent used for producing Parkinsonism in laboratory animals. The MPTP neurotoxicity in humans is irreversible and the consequential clinical and neurochemical features closely resemble those of the idiopathic Parkinson's disease. Therefore, handling of MPTP in laboratory may pose neurotoxic risk among researchers and animal caretakers. While it is well recognized that systemic administration of MPTP will cause Parkinsonian-like symptoms in humans and animals, it is not known whether similar neurological toxicity is transmittable and would develop in normal subjects housed closely with the MPTP-treated animals. In the present study, we treated mice daily with MPTP hydrochloride (30mg/kg, s.c.) for 5 consecutive days. In the same cage, a non-treated mouse (cagemate) was kept allowing for close physical interaction, free contact with the excreta, and sharing of food and water. Seventy-two hours after the treatment, the MPTP-treated mice and MPTP-exposed cagemates were analyzed for dopaminergic neurotoxicity comparing with the MPTP non-exposed control animals. We detected a significant number of TUNEL-positive cells, loss of tyrosine hydroxylase immunoreactivity in the substantia nigra, and depletion of dopamine in the striatum of MPTP-treated mice. However, these neurotoxic indices were not detected in the MPTP-exposed cagemates or MPTP non-exposed controls. Following each MPTP injection, approximately 42% of the chemical was excreted within 3h through the urine largely in the form of MPTP N-oxide, which is not expected to cross the blood-brain barrier and to cause dopaminergic toxicity in the brain when administered peripherally. These observations suggest that MPTP injections in mice do not transmit and cause Parkinsonian-like dopaminergic neurotoxicity in the neighboring normal cagemates through direct physical contact and exposure from the contaminated cage, food, water, and excreta.     

多聚ADP-核糖聚合酶抑制剂对帕金森病小鼠相关脑区病理变化的影响

目的研究帕金森病(Park inson’s d isease,PD)小鼠黑质和纹状体多巴胺(dopam inergic,DA)能神经元数量和超微结构的变化及多聚ADP-核糖聚合酶(poly(ADP-ribose)polym erase,PARP)抑制剂PJ34的干预作用。方法采用1-甲基-4-苯-1,2,3,6-四氢吡啶(1-m ethyl-4-phenyl-1,2,3,6-tetrahydropyrid ine,MPTP)制备PD小鼠模型,并用PJ34进行干预,2h、24h、72h进行酪氨酸羟化酶(tyrosine hydroxylase,TH)免疫组化染色观察DA能神经元数量,透射电镜观察超微结构改变。结果与正常对照小鼠比较,PD小鼠黑质TH阳性神经元进行性减少,核膜皱缩,染色质凝聚成块并有边聚现象;纹状体TH阳性神经纤维稀疏,突触数量减少。与PD小鼠比较,PJ34干预组黑质TH阳性神经元明显增多,纹状体TH阳性神经纤维密度增加(P<0.01),细胞形态比模型组明显改善。结论PARP的活性改变在PD的发病过程中发挥重要作用,PARP抑制剂对DA能神经元有保护作用。     

Protocatechuic acid inhibits neurotoxicity induced by MPTP in vivo

Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic neurons in substantia nigra (SN) with the presence of α-synuclein inclusions termed Lewy bodies. The neuroprotective effects of protocatechuic acid (PAc) both in vitro and in vivo have been reported. However, little is known about the effects of PAc on neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in vivo. In this study, we demonstrated that PAc inhibited the reduction of the latent periods in a rotarod test, and the contents of dopamine (DA) and its metabolites in striatum, and furthermore, it ameliorated the pathology in SN and the decreases in the expression of tyrosine hydroxylase (TH) in SN of C57BL/6J mice induced by MPTP. Taken together, our results indicate for the first time that PAc has neuroprotective effects on MPTP treated C57BL/6J mice and may be useful in clinical treatment of PD.     

银杏叶提取物对帕金森病模型小鼠多巴胺能神经元保护作用研究

目的研究银杏叶提取物（GBE）对帕金森病模型小鼠黑质（SN）多巴胺（DA）能神经元的保护作用。方法36只C5,Bk小鼠随机3组,每组12只。其中,帕金森病（PD）模型组的小鼠采用1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）腹腔注射（30mg／kg×5d）诱导PD;GBE预处理组的小鼠于注射MPTP前2h腹腔注射GBE（60mg／kg×8d）;正常对照组的小鼠只注射等体积生理氯化钠溶液。应用免疫组织化学染色观察小鼠黑质致密带（SNzc）酪氨酸羟化酶（TH）免疫反应阳性细胞数量的变化,用高效液相色谱法（HPLC-ECD）检测小鼠纹状体（Str）内DA及其代谢物二羟基苯乙酸（DOPAC）和高香草酸（HVA）含量。结果PD模型组小鼠SN内酪氨酸羟化酶（TH）阳性细胞数量、Str内DA及其代谢产物DOPAC和HVA的含量明显减少（P〈0．01）,GBE预处理组小鼠SN内TH阳性细胞数量、Str内DA及其代谢产物DOPAC和HVA的含量明显增多（P〈0.05）,但仍低于正常对照组（P〈0．01）。结论GBE对MPTP致帕金森病小鼠SNDA能神经元具有明显的保护作用。     

BDNF在Parkinson病小鼠的表达及丙戊酸盐对其影响的研究

为观察Parkinson病(PD)小鼠脑源性神经营养因子(BDNF)含量的变化及丙戊酸盐(valproate,VPA)对BDNF表达的影响,探讨VPA对PD病神经元的保护作用,本研究采用C57BL/6小鼠1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methy1-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)法建立PD模型。小鼠随机分为4组:盐水对照组(NS+NS)、模型组(NS+MPTP)、模型给药组(VPA+MPTP)和单独给药组(VPA+NS)。MPTP造模方法为每日颈部皮下注射MPTP(20 mg/kg),连续8 d。VPA在MPTP造模前1 d开始给药(400 mg/kg,i.p.),共14 d。单独给药组给予VPA,同时用等量的生理盐水代替MPTP。盐水对照组仅给予等量的生理盐水。采用原位分子杂交方法观察BDNF的表达,并对检测部位恒定视野内BDNF的阳性细胞进行灰度扫描和统计学分析。结果显示:与盐水对照组相比,模型组、模型给药组和单独给药组小鼠纹状体、海马、皮质内BDNF的表达均增强。该结果提示,PD小鼠神经元内BDNF增多,可能有利于受损神经元的修复;丙戊酸盐可能通过促进BDNF的表达而保护神经元。     

在小鼠帕金森病模型中观察丙戊酸钠对多巴胺神经元及GDNF表达的影响

目的:通过建立小鼠帕金森病模型,观察丙戊酸钠(valproate,VPA)对中脑黑质多巴胺神经元及胶质源性神经营养因子(glial-derived neurotrophic factor,GDNF)表达的影响,以期探索丙戊酸钠的神经保护作用机制.方法:采用免疫组织化学方法检测小鼠中脑黑质多巴胺神经元;原位杂交方法检测纹...