帕金森病模型大鼠黑质多巴胺能神经元的氧化应激研究

目的　探索帕金森病模型大鼠黑质多巴胺能神经元的氧化应激发病机制。方法　通过立体定位仪 ,将 6-OHDA注入大鼠一侧纹状体内制备 PD模型 ,2周后观察动物的行为学改变 ,2个月后观察黑质纹状体等的病理形态学变化 ,检测模型组、假手术组和正常对照组的超氧化物歧化酶 (SOD)的活性 ,丙二醛 (MDA)、一氧化氮(NO)代谢产物 (NO x)的含量的变化。结果　成功 PD模型鼠有 2 2只。光镜下 HE染色示模型组右侧黑质的多巴胺神经元受损 ,数目减少。模型组右侧黑质的 SOD的含量下降 ,MDA及 NO x含量明显升高 ,与左侧、假手术组及正常对照组相比有显著差异 (P>0 .0 5)。结论　 6-OHDA纹状体内双靶点注射法是一种有效的制备 PD模型的方法。帕金森病大鼠模型黑质内 SOD活性下降 ,MDA、NO x含量升高 ,氧化应激在 PD的发病中起重要的作用     

脑源性神经营养因子对帕金森病大鼠多巴胺能神经元的影响

目的观察脑源性神经营养因子对帕金森病(Parkinson’s disease,PD)大鼠模型黑质多巴胺能神经元的影响。方法选用Wistar种系大白鼠30只,体质量230~250g,随机分3组,通过左侧中脑黑质立体定向注射法,组1为生理盐水对照组(简称对照组)10只,注射相应量(5μL)的生理盐水;组2为注射6-OHDA制作帕金森病模型组(简称6-OHDA组)10只,注射6-OHDA,5μL(2μg/μL);组3为(6-OHDA+BDNF)组,在制成帕金森病模型后再向同侧中脑黑质注射BDNF 5μL(3μg/5μL),连续6d,1次/d。分别观察动物的旋转行为,免疫组化染色方法观察黑质酪氨酸羟化酶(tyrosine hydroxylase,TH)阳性神经元的数量,高效液相法测定纹状体部多巴胺(dopamine,DA)含量的变化。结果单侧黑质内注入6-OHDA制成帕金森病大鼠模型后,6-OHDA组与对照组比较,产生旋转行为,(6-OHDA+BDNF)组在观察旋转行为时,症状明显改善;镜下见TH阳性神经元主要见于对照组的黑质致密部,数量为(42.3±7.56)个/μm2,模型组黑质致密部TH阳性神经元数明显减少为(2.41±1.07)个/μm2,(6-OHDA+BDNF)组黑质致密部TH阳性神经元数为(15.36+3.04)个/μm2;纹状体部多巴胺含量:生理盐水组为(11.4±1.2)μg/g,6-OHDA组(3.6±0.5)μg/g,(6-OHDA+BDNF)组(5.5±0.6)μg/g。结论 BDNF能改善6-OHDA所致的帕金森病大鼠黑质多巴胺能神经元数目的减少;明显抑制6-OHDA引起的纹状体部多巴胺含量降低;并可抑制6-OHDA对黑质多巴胺能神经元的毒性作用。     

帕金森病大鼠胃肠功能障碍的机制

目的 探讨6-羟基多巴胺(6-OHDA)诱导的SD大鼠帕金森病(PD)模型胃肠功能障碍的发生机制.方法 60只SD大鼠随机分为6-OHDA组和对照组;以6-OHDA诱导制备PD大鼠模型.4周后收集大鼠1h粪便排出量,计算粪便含水量,测定餐后2 h大鼠胃内固体食物残留率.采用免疫组化法检测黑质酪氨酸羟化酶(TH)、胃肠神经丛α-突触核蛋白(α-syn)、神经元型一氧化氮合酶(nNOS)的表达;应用逆转录(RT)-PCR方法检测胃、结肠组织nNOS mRNA的表达.结果 与对照组相比,6-OHDA组大鼠1 h粪便排出量及含水量明显降低,胃内固体食物残留率明显增加(均P<0.01);损伤侧黑质TH阳性细胞明显减少(P<0.01);胃肠肌间神经丛α-syn表达明显升高,nNOS表达明显降低(均P<0.01);胃肠组织nNOS mRNA表达明显降低(均P<0.01).结论 PD大鼠胃肠功能障碍可能与胃肠神经系统nNOS水平降低有关.     

神经细胞黏附分子在GDNF保护大鼠多巴胺能神经元中的作用

目的研究神经细胞黏附分子(neural cell adhesion molecule,NCAM)在胶质细胞系源性神经营养因子(glial cell line-derived neurotrophic factor,GDNF)保护帕金森(Parkinson's disease,PD)模型大鼠受损多巴胺(dopamine,DA)能神经元中的作用。方法右侧纹状体内立体定位注射6-羟多巴胺(6-OHDA)制备早期PD模型,而后分为4组:对照组(同侧黑质内注射PBS)、NCAM组(同侧黑质内仅注射anti-NCAM抗体)、GDNF组(同侧黑质内注射GDNF)、NCAM阻断组(同侧黑质内注射anti-NCAM抗体30min后注射GDNF),采用免疫组织化学染色技术和免疫印迹技术,观察各组酪氨酸羟化酶(tyrosine hydroxylase,TH)的表达变化。结果GDNF组黑质致密部TH阳性神经元数目及表达的量明显多于PBS组,差别有统计学意义;NCAM阻断组与GDNF组相比,该处TH阳性神经元数目及表达的量明显减少,差别有统计学意义。结论NCAM参与了GDNF保护DA能神经元的作用。     

偏侧帕金森病猴模型黑质和纹状体一氧化氮合酶表达的变化

目的探讨偏侧帕金森病（PD）猴模型黑质和纹状体一氧化氮合酶（NOS）表达的变化。方法对3只恒河猴经单侧颈内动脉注射1-甲基4-苯基1,2,3,6-四氢吡啶（MPTP）制备成偏侧PD猴模型后,应用还原型尼克酰胺腺嘌呤二核苷酸-黄递酶（NADPH．d）组化染色方法观察偏侧PD猴黑质和纹状体NOS阳性神经元表达的变化,并与正常猴比较。结果偏侧PD猴MPTP毁损侧的黑质和纹状体的NOS阳性神经元数目较毁损对侧和正常猴明显增加（均P〈0．01）,毁损对侧的黑质和纹状体NOS阳性神经元数目与正常猴比较差异无统计学意义。结论偏侧PD猴黑质和纹状体NOS阳性神经元增多,由此引起一氧化氮（NO）合成和释放增多,可能对黑质和纹状体神经元的变性和死亡起重要作用。     

镁对帕金森病大鼠黑质多巴胺神经元的影响

目的观察镁对帕金森病(PD)大鼠黑质多巴胺神经元影响及其作用机制。方法应用6-羟基多巴胺(6-OHDA)制备偏侧PD大鼠模型后分为硫酸镁组、美多巴组、混合组(硫酸镁+美多巴)和对照组(生理盐水),并给予相应药物灌胃治疗28d。观察治疗后各组大鼠旋转行为的变化;免疫组化法检测黑质酪氨酸羟化酶(TH)阳性神经元数量;生化法测定损毁侧纹状体超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)含量;逆转录聚合酶链反应检测损毁侧黑质caspase-3 mRNA表达;Western Blot法检测核因子(NF)-кBP65水平。结果治疗后仅混合组出现较稳定的向对侧的旋转行为;TH阳性神经元数混合组较其他各组明显增加(均P<0.05);与对照组和美多巴组比较,硫酸镁组和混合组SOD、GSH-Px活性显著增高,MDA、caspase-3 mRNA、NF-кBP65水平显著降低(均P<0.05);硫酸镁组与混合组间差异无统计学意义。结论镁及美多巴联合治疗可提高PD模型脑内多巴胺神经元存活、降低氧化应激损伤、减少神经元凋亡,改善PD大鼠症状。     

脂多糖对多巴胺能神经元的损毁作用及其机制研究

目的观察脂多糖(1ipopolysaccharide．LPs)对黑质多巴胺(dopamine，DA)能神经元的损毁作用，探讨免疫机制与帕金森病(Parkinsondisease，PD)发病的相关性。方法采用立体定向术将LPS注人大鼠单侧黑质后分别于注射后2、3、4周经腹腔注射阿朴吗啡诱发动物旋转行为；采用高效液相色谱一电化学法(high performanee liquid chromatography，HPLC)测定纹状体和黑质部位DA等单胺类递质含量；采用免疫组化法检测黑质酪氨酸羟化酶(tyrosine hydroxylase，TH)阳性细胞数；采用尼(氏)染色(Nissl)观察小胶质细胞的活化和以双重免疫酶染色法观察小胶质细胞活化和诱导型一氧化氮合酶(inducible nitric oxide，iNOS)合成。结果大鼠单侧黑质注人LPS后2、3、4周，以阿朴吗啡诱发大鼠均出现旋转行为，其损伤侧纹状体和黑质DA及其代谢物含量降低了30%～70%，注射侧的黑质TH阳性细胞数减少，尤以3周和4周为甚．尼(氏)染色和双重免疫酶染色法也分别显示LPS注射侧小胶质细胞活化，同时伴有iNOS合成的增加。结论LPS对DA能神经元具有一定的损毁作用，小胶质细胞的活化及其释放的NO有可能参与该细胞死亡，提示免疫机制与PD的发病可能存在相关性。     

左旋多巴对帕金森病大鼠黑质多巴胺能神经元及纹状体多巴胺递质的影响

目的　研究长期应用左旋多巴对帕金森病 (PD)大鼠黑质多巴胺 (DA)能神经元和DA递质的影响。方法　采用 6 羟基多巴胺 (6 OHDA)制备部分损毁和严重损毁的PD大鼠模型 ,给两种模型口服不同剂量左旋多巴 /苄丝肼 3个月 ,通过观察大鼠旋转行为、酪氨酸羟化酶 (TH)免疫组化染色和高效液相色谱 电化学检测仪 (HPLC ECD)检测纹状体单胺类递质 ,研究左旋多巴对PD大鼠残存的黑质DA能神经元的影响。结果　 (1)左旋多巴对PD大鼠的旋转行为无明显影响 ;(2 )TH阳性细胞数损毁侧 /非损毁侧比值在左旋多巴喂药组和不喂药对照组的差异无显著意义 (P >0 0 5 ) ;(3)在严重损毁组 ,大剂量左旋多巴使PD大鼠损毁侧DA和 3,4二羟基苯乙酸 (DOPAC)水平明显升高(P <0 0 1)。结论　长期使用左旋多巴对 6 OHDA单侧损毁的PD大鼠残存的黑质DA能神经元无毒性作用。     

立体定向技术注射6-OHDA至内侧前脑束建立帕金森病大鼠模型

目的 建立大鼠帕金森病模型,观测其行为学和多巴胺能神经元的变化.方法 利用立体定向技术,注射6-OHDA至大鼠脑的内侧前脑束,于注射后2、4、6、8周观测阿朴吗啡诱导的大鼠旋转行为学变化;采用免疫组化染色检测TH的表达,了解中脑黑质多巴胺能阳性神经元变化.结果 所有大鼠分别于第2、4、6、8周的进行阿朴吗啡诱导旋转行为测试,67只大鼠中出现16只大鼠(23.8%)旋转圈数＞7r/min,并且＞210r/30min,为合格的PD大鼠模型.第8周时,大鼠旋转次数平均为10.48±1.91/分.免疫组化检测,成功模型光镜下分别计数双侧黑质TH阳性神经元,损毁侧黑质TH阳性神经元占正常侧的3.8%,即毁损侧TH阳性神经元减少96.2%.结论 利用立体定向技术,选择内侧前脑束为靶点,可建立6-OHDA大鼠PD模型.     

6-羟基多巴胺单侧纹状体注射对大鼠双侧多巴胺能神经元的影响

目的探讨帕金森病大鼠模型中6-羟基多巴胺（6-OHDA）单侧纹状体注射对双侧黑质纹状体多巴胺能神经元的影响。方法大鼠随机分成模型组和对照组，模型组自一侧纹状体注射6-OHDA，对照组注射PBS；用免疫组织化学方法分别检测大鼠双侧黑质和纹状体区酪氨酸羟化酶（TH）阳性细胞和纤维的表达；高效液相色谱检测双侧纹状体多巴胺（DA）及其代谢产物3，4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）含量。结果模型组大鼠双侧（毁损侧与其对侧）黑质致密区TH阳性细胞数量均少于对照组（P〈0．01），模型组双侧纹状体区TH阳性纤维密度均低于对照组；模型组大鼠双侧纹状体区DA含量均低于对照组（P〈0．01）；双侧DOPAC和HVA含量也降低。结论6-羟多巴胺单侧纹状体注射制作的帕金森病大鼠模型的对侧黑质纹状体也有损伤。     

一氧化氮与帕金森病大鼠模型神经损伤的研究

目的 研究一氧化氮（ＮＯ）在帕金森病（ＰＤ）大鼠模型神经损伤中的作用。方法 用高效液相色谱电化学法（ＨＰＬＣ－ＥＴ）及还原型辅酶Ⅱ（ＮＡＤＰＨ）黄递酶组化法观察ＮＯ在ＰＤ大鼠模型神经损伤中的作用。结果 神经型一氧化氮合成酶（ｎＮＯＳ）抑制剂７－硝基吲唑（７－ＮＩ）明显减少６－羟基多巴胺（６－ＯＨＤＡ）引起的纹状体多巴胺及其代谢产物的降低（Ｐ〈０．０１）；纹状体ＮＡＤＰＨ黄递酶阳性神经元可抵抗６－Ｏ     

谷胱甘肽对黑质多巴胺能神经元保护作用的研究

目的　探讨谷胱甘肽对多巴胺能神经元保护作用。方法　用还原型谷胱甘肽和 6 羟多巴胺孵育大鼠脑片 1小时 ,用抗酪氨酸羟化酶免疫组织化学法观察黑质阳性神经元胞体及突起的变化。结果　 6 羟多巴胺使脑片黑质酪氨酸羟化酶阳性神经元突起明显减少 ,而胞体不变 ;谷胱甘肽单独不影响多巴胺能神经元 ,但却阻止 6 羟多巴胺引起的神经元突起减少。结论　谷胱甘肽能阻止 6 羟多巴胺导致的多巴胺能神经元的变性 ,对多巴胺能神经元具有保护作用     

Characterization of a new low‐dose 6‐hydroxydopamine model of Parkinson's disease in rat

Intrastriatal administration of 6‐hydroxydopamine (6‐OHDA) induces partial degeneration of the nigrostriatal pathway, mimicking the pathology of Parkinson's disease (PD). Setting up the partial lesion model can be challenging because a number of experimental settings can be altered. This study compares seven experimental settings in a single study on d‐amphetamine‐induced rotations, tyrosine hydroxylase (TH)‐positive neurites in the striatum, dopamine transporter (DAT)‐positive neurites in the striatum, and TH‐positive cells in the substantia nigra pars compacta (SNpc) in rats. Moreover, we validate a new algorithm for estimating the number of TH‐positive cells. We show that the behavior and immunoreactivity vary greatly depending on the injection settings, and we categorize the lesions as progressive, stable, or regressive based on d‐amphetamine‐induced rotations. The rotation behavior correlated with the degree of the lesion, analyzed by immunohistochemistry; the largest lesions were in the progressive group, and the smallest lesions were in the regressive group. We establish a new low‐dose partial 6‐OHDA lesion model in which a total of 6 μg was distributed evenly to three sites in the striatum at a 10° angle. The administration of low‐dose 6‐OHDA produced stable and reliable rotation behavior and induced partial loss of striatal TH‐positive and DAT‐positive neurites and TH‐positive cells in the SNpc. This model is highly suitable for neurorestoration studies in the search for new therapies for PD, and the new algorithm increases the efficacy for estimating the number of dopamine neurons. This study can be extremely useful for laboratories setting up the partial 6‐OHDA model. © 2016 Wiley Periodicals, Inc.     

阿朴吗啡对颈动脉体球细胞帕金森病大鼠纹状体移植区C-FOS和JUN-B表达的影响

目的 :探讨帕金森病 (PD)大鼠颈动脉体球细胞移植治疗后多巴胺细胞的功能状况。方法 :采用 6 -羟多巴胺损毁制备 PD大鼠模型 ,腹腔注射阿朴吗啡 2 h后诱导移植后 12周纹状体组织内 c- fos和 Jun- B的表达 ,分析其分布和阳性细胞数目。结果 :移植后 12周 ,移植物内和与宿主接触面 c- fos表达增高 ,而 Jun- B的表达没有变化。结论 :移植物内和与宿主接触面 c- fos表达增高表明移植细胞仍保持着其生理功能     

Developing patterns of nitric oxide synthesizing neurons in the rat striatum: histochemical analysis

The prenatal and postnatal development of NADPH-diaphorase (NADPH-d)/neuronal nitric oxide synthase (nNOS) positive neurons was studied in the striatum of rats. NADPH-d was demonstrated enzyme histochemically and nNOS immunohistochemically using a polyclonal antibody. NADPH-d neurons appeared in the ventrolateral part of the striatum on embryonic day 18 (E18). Thereafter, the number of NADPH-d neurons increased and began to distribute homogeneously in the striatum. The density of NADPH-d neurons became highest at postnatal day 5 (P5) and then decreased as the volume of the striatum continued to increase. The number of NADPH-d neurons reached its peak around 3-4 weeks after birth. The sizes of NADPH-d neurons were measured. The NADPH-d neurons grew larger until P14 (mean area 260 microm(2)) and became smaller thereafter (mean area 170 microm(2)). Patches of high NADPH-d activity and tyrosine hydroxylase (TH) immunoreactivity were also examined in the developing striatum. The distributions of NADPH-d patches overlapped with those of TH-immunoreactive patches by P10. The spatiotemporal appearance of nNOS and overlapping of nNOS patchy distribution with TH point to an important role of NO and to an interaction between nNOS and DA fibers during development of the striatum.     

帕金森病大鼠黑质NurrlmRNA表达的动态变化

目的　探讨帕金森病大鼠黑质核内受体相关因子 1(Nurr1)mRNA表达的动态变化。方法　通过脑立体定位注射 6 羟基多巴胺 (6 OHDA)的方法建立大鼠帕金森病 (Parkinson’sdisease,PD)模型 ,采用HE染色 ,酪氨酸羟化酶 (TH)免疫组织化学染色、原位杂交技术 ,选择 6 OHDA注射术后 1d、3d、5d、7d、2 1d为研究时点 ,观察大鼠PD模型形成过程中黑质TH 多巴胺细胞数量及Nurr1mRNA表达的改变。结果　与健侧比较 ,注射 6 OHDA 5d组损毁侧黑质TH 细胞显著减少 (P <0 .0 1) ,2 1d时仅为健侧的 15 %且出现明显的旋转行为 ;同时 ,注射 6 OHDA 1d组损毁侧黑质Nurr1mRNA表达即开始下降 ,且以 3d组最为显著 (P <0 .0 1) ,7d以后各组完全消失。结论　本实验研究结果表明 ,6 OHDA能下调大鼠黑质Nurr1mRNA的表达早于诱导多巴胺细胞的死亡     

Evaluating the Role of Neuronal Nitric Oxide Synthase-Containing Striatal Interneurons in Methamphetamine-Induced Dopamine Neurotoxicity

Production of nitric oxide (NO) has been implicated in methamphetamine (METH)-induced dopamine (DA) neurotoxicity. The source of this NO has not been clearly delineated, but recent evidence suggests that it arises from activation of neuronal nitric oxide synthase (nNOS), which is selectively expressed in a subpopulation of striatal interneurons. Our objective was to determine whether inhibiting activation of nNOS-containing interneurons in the striatum blocks METH-induced neurotoxicity. These interneurons selectively express the neurokinin-1 (NK-1) receptor, which is activated by substance P. One particular toxin, a conjugate of substance P to the ribosome-inactivating protein saporin (SSP–SAP), selectively destroys neurons expressing the NK-1 receptor. Thus, we examined the extent to which depletion of the nNOS-containing interneurons alters production of NO and attenuates METH-induced neurotoxicity. The SSP–SAP lesions resulted in significant loss of nNOS-containing interneurons throughout striatum. Surprisingly, this marked deletion did not confer resistance to METH-induced DA neurotoxicity, even in areas devoid of nNOS-positive cells. Furthermore, these lesions did not attenuate NO production, even in areas lacking nNOS. These data suggest that nNOS-containing interneurons either are not necessary for METH-induced DA neurotoxicity or produce NO that can diffuse extensively through striatal tissue and thereby still mediate neurotoxicity.     

Methamphetamine administration causes overexpression of nNOS in the mouse striatum

The accumulated evidence suggests that the overproduction of nitric oxide (NO) is involved in methamphetamine (METH)-induced neurotoxicity. Using NADPH-diaphorase histochemistry, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) antibody immunohistochemistry, the possible overexpression of nNOS and iNOS was investigated in the brains of mice treated with METH. The number of positive cells or the density of positive fibers was assessed at 1 h, 24 h and 1 week after METH injections. There were no clear positive iNOS cells and fibers demonstrated in the brains of mice after METH treatment. In contrast, METH caused marked increases in nNOS in the striatum and hippocampus at 1 and 24 h post-treatment. The nNOS expression normalized by 1 week. There were no statistical changes in nNOS expression in the frontal cortex, the cerebellar cortex, nor in the substantia nigra. These results provide further support for the idea that NO is involved in the neurotoxic effects of METH.     

Role of nitric oxide synthase against MPTP neurotoxicity in mice

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic pathway injury similar to that observed in Parkinson's disease. Many hypotheses have been proposed to explain the mechanisms underlying MPTP neurotoxicity. Previous work showed that the inhibitor of neuronal nitric oxide synthase (nNOS) might produce protection against MPTP-induced dopaminergic toxicity. To exactly test the role of NO in MPTP neurotoxicity, we examined the effect of nNOS inhibitor 7-nitroindazole, in comparison with that of nonselective NOS inhibitor (L-NAME), immunosuppressant (FK-506), monoamine oxidase (MAO) inhibitors (clorgyline and pargyline), N-methyl-D-aspartate receptor antagonist (MK-801) and Ca2+ antagonist (amlodipine). Among seven compounds, 7-nitroindazole produced dose-dependent protection against MPTP-induced depletion of striatal dopamine and its metabolite 3,4-dihydroxyphenyl acetic acid (DOPAC) in mice. Clorgyline and pargyline also showed a significant effect on MPTP-induced dopamine depletion in the mouse striatum. However, both compounds did not protect against MPTP-induced depletion of striatal DOPAC Our immunohistological study with tyrosine hydroxylase (TH) and microtuble-associated protein 2 (MAP 2) showed that 7-nitroindazole or pargyline can protect against MPTP-induced depletion of TH and MAP 2 immunostained neurons in the substantia nigra. Furthermore, these compounds reduced a marked increase in GFAP-positive astrocytes of the mouse striatum after MPTP treatments. The present study demonstrates that nNOS inhibitor 7-nitroindazole as well as MAO inhibitors clorgyline and pargyline can produce dose-dependent neuroprotection against the dopaminergic neurotoxicity of MPTP. However, nonselective NOS inhibitor L-NAME, immunosuppressant FK-506, NMDA receptor antagonist MK-801 and Ca2+ antagonist amlodipine did not show a beneficial effect on MPTP neurotoxicity.     

The 6‐hydroxydopamine‐induced nigrostriatal neurodegeneration produces microglia‐like NG2 glial cells in the rat substantia nigra

Neuron/glial 2 (NG2)‐expressing cells are often referred to as oligodendrocyte precursor cells. NG2‐expressing cells have also been identified as multipotent progenitor cells. However, microglia‐like NG2 glial cells have not been fully examined in neurodegenerative disorders such as Parkinson's disease (PD). In the present study, we chose two rat models of PD, i.e., intranigral or intrastriatal injection of 6‐hydroxydopamine (6‐OHDA), since the cell bodies of dopamine (DA) neurons, which form a nigrostriatal pathway, are in the substantia nigra pars compacta (SNpc) while their nerve terminals are in the striatum. In the nigral 6‐OHDA‐injected model, activated NG2‐positive cells were detected in the SNpc but not in the striatum. In contrast, in the striatal 6‐OHDA‐injected model, these cells were detected in both the SNpc and the striatum. In both models, activated NG2‐positive cells were located close to surviving tyrosine hydroxylase (TH)‐positive neurons in the SNpc. In addition, activated NG2‐positive cells in the SNpc coexpressed ionized calcium‐binding adaptor molecule 1 (Iba1), a microglia/macrophage marker. Interestingly, these double‐positive glial cells coexpressed glial cell line‐derived neurotrophic factor (GDNF). These results suggest that microglia‐like NG2 glial cells may help protect DA neurons and may lead to new therapeutic targets in PD. © 2010 Wiley‐Liss, Inc.