Notch1信号系统在氟西汀上调大鼠海马神经再生中的作用

目的 了解慢性氟西汀干预正常大鼠所导致的海马神经再生上调与Notch1信号系统功能改变的关系.方法 应用大鼠腹腔注射氟西汀建立在体模型,分为对照组、14 d干预组、28 d干预组(n=12),采用免疫组化、real time PCR和Western blot,测定大鼠海马神经干细胞的增殖、存活和分化以及Notch1信号通路各个因子(NICD、Hes1、Hes5、Jag1)的基因及蛋白表达水平的改变.结果 ①与对照组(2919.50±188.80)比较,14 d氟西汀干预组(3706.50±228.04)、28 d氟西汀干预组(4334.33±217.48)海马齿状回神经干细胞增殖明显增加(P<0.001);与对照组(2404.50±148.77)相比,Flu干预28 d组(3273.16±156.68)海马齿状回神经干细胞存活明显增加(P<0.001);与对照组比较,氟西汀干预组NeuN/BrdU、GFAP/BrdU比例无明显差异(P＞0.05).②与对照组[NICDmRNA (0.30±0.03),Hes1mRNA (0.53±0.03),Hes5mRNA (0.21±0.02),Jag1mRNA(1.04±0.07)]比较,氟西汀(Flu)干预14d组[NICDmRNA (0.45±0.05),Hes1mRNA (0.65±0.06),Hes5mRNA (0.31±0.06),Jag1mRNA(2.46±0.39)]和Flu干预28 d组[NICDmRNA (0.42±0.03),Hes1mRNA (0.85±0.06),Hes5mRNA (0.39±0.02),Jag1mRNA(3.21±0.34)]Notch1信号通路各因子基因水平均明显升高(P<0.01或P<0.001).③与对照组[NICD(2.36±0.17),Hes1(1.09±0.25),Jag1(2.33±0.31)]比较,Flu干预14 d组[NICD(3.20±0.25),Jag1(2.86±0.25)]和Flu干预28 d组[NICD(3.40±0.19),Hes1(1.43±0.13),Jag1(3.35±0.14)]NICD、Hes1、Jag1蛋白水平明显升高,差异有统计学意义(P<0.01或P<0.001).与对照组Hes5比较,Flu干预14 d组Hes5和Flu干预28 d Hes5蛋白水平无改变,差异无统计学意义(P＞0.05).结论 氟西汀促进大鼠海马齿状回神经干细胞的增殖和存活,但对分化无影响;同时,海马Notch信号功能激活,提示Notch1信号系统可能参与氟西汀介导的大鼠海马神经再生上调.     

抑郁状态下大鼠海马Notch1信号系统的改变

目的 了解大鼠抑郁模型中海马神经重塑障碍与Notch1信号系统功能改变的关系.方法 54只大鼠随机分为CUMS 14 d组、CUMS 28 d组和对照组,前两组接受慢性不可预知温和应激和孤养(chronic unpredictable mild stress,CUMS)14 d和28 d建立抑郁模型.采用免疫组化、免疫荧光、RT-PCR和Western blot 法.测定大鼠海马神经干细胞的增殖、存活和分化以及Notch1信号通路各个因子的基因及蛋白表达水平的改变.结果 与对照组比较,CUMS 14 d组和CUMS 28 d组大鼠海马神经干细胞增殖与存活明显减少(P<0.001).CUMS 28 d组大鼠海马神经干细胞分化NeuN/BrdU、GFAP/BrdU比例无明显差异(P>0.05).与对照组比较.CUMS 14 d组和CUMS 28 d组Notch1信号通路各因子(NICD、Hes1、Hes5和Jag1)基因表达和蛋白水平明显降低(P<0.01).结论 抑郁大鼠海马齿状回神经干细胞增殖和存活受到抑制,但分化无改变;同时,大鼠海马Notch1功能下调.提示Notch1信号系统可能与抑郁症海马神经再生障碍有关.     

慢性应激及氟西汀治疗后大鼠海马细胞支架的改变

目的 探讨慢性不可预见性应激及氟西汀治疗后大鼠细胞支架微管系统的动态性变化及其可能机制.方法 将24只大鼠按随机数字表法分为对照组(空白对照+生理盐水)、慢性不可预见性温和应激(CUMS)组(CUMS+生理盐水)和氟西汀组(CUMS+氟西汀),每组8只.对大鼠进行连续21 d CUMS后,氟西汀组给予氟西汀(10 mg/kg)治疗21 d,对照组和CUMS组给予生理盐水.实验结束后进行行为学观察,并使用免疫印迹法(western blot)检测大鼠海马乙酰化微管蛋白(Acet-Tub),酪氨酸化微管蛋白(Tyr-Tub),微管结合蛋白2(MAP-2)及磷酸化微管结合蛋白2(phospho-MAP-2).结果 (1)CUMS组糖水偏好[(55.13±11.80)%],总行程[(2736.59±511.20)cm],运动平均速度[(5.69±1.08)cm/s]及直立次数[(2.50±2.00)次]均低于对照组,差异有统计学意义(P＜0.01);氟西汀组上述指标与对照组比较差异无统计学意义(P＞0.05).(2)CUMS组与对照组相比,Acet-Tub表达升高[(171.84±10.34)%],Tyr-Tub[(62.06±9.24)%]和phospho-MAP-2[(68.81±8.93)%]的表达降低,差异有统计学意义(P均＜0.01),MAP-2的表达与对照组比较无统计学意义(P＞0.05);经氟西汀治疗后,Acet-Tub的表达降低为[(96.18±8.92)%],Tyr-Tub和phospho-MAP-2的表达分别升高为[(95.06±8.00)%]、[(100.60±7.30)%],与对照组比较均无统计学意义(P＞0.05).结论 慢性应激后微管动态性减低,神经可塑性受损,氟西汀可以逆转海马的这些损伤,上述过程可能与微管相关蛋白磷酸化水平的变化有关.     

Phenotypic changes of Schwann cells on the proximal stump of injured peripheral nerve during repair using small gap conduit tube

Dedifferentiation of Schwann cells is an important feature of the response to peripheral nerve injury and specific negative myelination reg-ulators are considered to have a major role in this process. However, most experiments have focused on the distal nerve stump, where the Notch signaling pathway is strongly associated with Schwann cell dedifferentiation and repair of the nerve. We observed the phenotypic changes of Schwann cells and changes of active Notch signaling on the proximal stump during peripheral nerve repair using small gap conduit tubulization. Eighty rats, with right sciatic nerve section of 4 mm, were randomly assigned to conduit bridging group and control group (epineurium suture). Glial fibrillary acidic protein expression, in myelinating Schwann cells on the proximal stump, began to up-reg-ulate at 1 day after injury and was still evident at 5 days. Compared with the control group, Notch1 mRNA was expressed at a higher level in the conduit bridging group during the first week on the proximal stump. Hes1 mRNA levels in the conduit bridging group significantly increased compared with the control group at 3, 5, 7 and 14 days post-surgery. The change of the Notch intracellular domain shared a simi-lar trend as Hes1 mRNA expression. Our results confirmed that phenotypic changes of Schwann cells occurred in the proximal stump. The differences in these changes between the conduit tubulization and epineurium suture groups correlate with changes in Notch signaling.This suggests that active Notch signaling might be a key mechanism during the early stage of neural regeneration in the proximal nerve stump.     

应激及再应激后大鼠大脑皮质BDNF及细胞支架的改变

目的 研究慢性不可预见性温和应激（CUMS）,氟西汀治疗及再应激后大鼠大脑皮质脑源性神经营养因子（BDNF）及细胞支架微管系统的改变.方法 将32只大鼠随机分为4组：对照组（空白对照＋o.9％氯化钠溶液）,CUMS组（CUMS＋0.9％氯化钠溶液）,氟西汀组（CUMS＋氟西汀）,再应激组（CUMS＋氟西汀＋1周药物清洗期＋CUMS）.大鼠进行21 d CUMS后,氟西汀组给予氟西汀治疗21d,再应激组给予氟西汀治疗21d后进行1周药物清洗,再次给予CUMS.其余两组给予0.9％氯化钠溶液.实验结束后检测糖水偏好,并使用Western Blotting检测鼠大脑总皮质及额叶皮质Acet-Tub,Tyr-Tub,BDNF,总tau,磷酸化tau（Ser356及Thr231）的表达.结果 21 d慢性应激后,CUMS组糖水偏好（52.37±16.758）％与对照组（76.37±7.671）％比较差异有统计学意义（P＜0.01）;氟西汀组糖水偏好与对照组比较差异无统计学意义;CUMS再应激组糖水偏好（42.00±8.03）％与对照组及CUMS组比较差异均有统计学意义（P＜0.01）.与对照组比较,CUMS组大鼠额叶皮质Acet-Tub表达升高（174.53±13.7）,Tyr-Tub表达降低（64.00±9.24）,BDNF表达降低（67.94±9.81）,p-tau（Ser356）的表达（165.49±9.68）及p-tau（Thr231）的表达（210.83±23.12）升高,差异有统计学意义（P＜0.01）.经氟西汀治疗后,Acet-Tub表达降低,Tyr-Tub、BDNF的表达升高,p-tau（Ser356）及p-tau（Thr231）的表达降低,与对照组比较差异无统计学意义.再应激组Acet-Tub表达升高（250.46±15.72）,Tyr-Tub表达降低（33.54±10.23）,BDNF表达降低（34.77±6.24）,p-tau （Ser356）表达（237.42±10.24）及p-tau（Thr231）的表达（373.69±34.14）升高,与对照组及CUMS组比较差异均有统计学意义（P＜0.01）.4组之间总tau的表达比较差异无统计学意义.大鼠大脑总皮质各项指标差异无统计学意义.结论 抑郁动物模型大脑额叶皮质微管动态性减低,伴随BDNF表达减低     

氟西汀对大鼠星形胶质细胞分泌的胶质源性神经营养因子的影响

目的 探讨氟西汀对大鼠星形胶质细胞分泌的胶质源性神经营养因子(GDNF)的影响.方法 以氟西汀干预体外培养的大鼠海马星形胶质细胞,通过四甲基偶氮唑盐法(MTT)检测不同浓度氟西汀对细胞活力的影响;采用酶联免疫吸附测定法(ELISA)检测细胞培养液GDNF浓度及Real-time PCR法检测GDNFmRNA的表达.结果 (1)氟西汀浓度超过35 μmol/L浓度时,可降低细胞活性,差异有统计学意义(P<0.01或P<0.05);(2)10 μmol/L氟西汀干预星形胶质细胞不同时间后,48 h组细胞培养液GDNF浓度[(68±13)fg/L]高于0 h组[(32±11)fg/L]、6 h组[(34±12)fg/L]、12 h组[(41±17)fg/L]、24 h组[(45±13)fg/L],差异均有统计学意义(P均<0.01);(3)不同浓度氟西汀作用星形胶质细胞48 h后,10 μmol/L浓度组的细胞培养液GDNF浓度[(64±17)fg/L]高于0 μmol/L[(39±15)fg/L]和1 μmoVL浓度组[(39±18)fg/L],差异均有统计学意义(P均<0.05);(4)氟西汀作用星形胶质细胞48 h后,撤离氟西汀24 h后星形胶质细胞仍明显分泌GDNF,差异有统计学意义(P<0.01或P<0.05);(5)不同浓度氟西汀作用星形胶质细胞24 h后,10 μmol/L和20 μmol/L浓度组细胞GDNFmRNA表达量[分别为(0.008 1±0.001 1)和(0.006 3±0.000 3)]高于0 μmol/L、1 μmol/L及5 μmol/L浓度组[分别为(0.003 1±0.000 7)、(0.003 9±0.000 3)和(0.004 1±0.000 2)],差异均有统计学意义(P均<0.01).结论 氟西汀可能通过促进星形胶质细胞GDNF的分泌来发挥其神经保护作用.     

氟西汀与体感振动音乐疗法联合疗法治疗脑卒中后抑郁的临床效果及其对神经功能缺损的影响

目的探讨氟西汀与体感振动音乐疗法联合治疗脑卒中后抑郁的临床疗效,并分析患者神经功能缺损与抑郁状态的变化。方法选取100例脑卒中后抑郁患者按照随机数字表法分为联合组与对照组,对照组氟西汀治疗,联合组给予氟西汀与体感振动音乐疗法联合治疗,对两组患者神经功能缺损与抑郁状况进行对比观察。结果治疗前,联合组与对照组汉密尔顿抑郁量表(Hamilton Depression Scale,HAMD)评分(24.89±3.16 vs 25.23±3.05)差异无统计学意义(P0.05);治疗后,联合组与对照组脑卒中神经功能缺损状态评分(the National Institutes of Health Stroke Scale,NIHSS)(11.73±1.89vs17.03±2.66)差异有统计学意义(P0.05);治疗前,联合组与对照组NIHSS评分(17.11±2.31vs17.04±2.52)差异无统计学意义(P0.05);治疗后,联合组与对照组NIHSS评分(8.05±1.13vs13.25±1.83)差异有统计学意义(P0.05)。结论临床中对于脑卒中后抑郁患者给予氟西汀与体感振动音乐疗法联合治疗效果明显,且对改善患者抑郁状态和神经功能缺损状况有着显著的作用,值得应用推广。     

下丘脑NK2受体在应激介导抑郁症发生中的作用

目的 阐明神经激肽A的受体NK2在慢性不可预见性温和刺激(CUMS)所致的抑郁样行为发生、发展中的可能作用和机制.方法 SD大鼠随机分为对照组、氟西汀组和抑郁模型组3组,行为学检测后,氟西汀组和抑郁模型组均给予孤养+CUMS造成大鼠抑郁症模型,再次行为学检测后,氟西汀组大鼠给予氟西汀腹腔注射21d,抑郁模型组给予同体积生理盐水腹腔注射21d,再次进行行为学检测,麻醉后取大鼠下丘脑,提取组织mRNA和蛋白后,采用荧光定量PCR技术和Western Blot技术检测NK2的表达.结果 应激前3组大鼠的糖水偏好率和强迫游泳的不动时间均无统计学意义.应激后,氟西汀组和抑郁模型组大鼠的糖水摄入明显减少、强迫游泳不动时间明显增长,差异均有统计学意义(P＜0.05).而给予氟西汀后,氟西汀组大鼠的糖水偏好率有所增加,强迫游泳的不动时间有所减少,与对照组比较差异无统计学意义(P＞0.05),但与抑郁组大鼠相比,差异均有统计学意义(P＜0.05).与对照组和氟西汀组比较,抑郁组下丘脑NK2受体的mRNA和蛋白的表达量明显升高,差异有统计学意义(P＜0.05),而氟西汀组与对照组相比差异无统计学意义(P＞0.05).结论 CUMS可引起大鼠行为学改变,造成大鼠抑郁模型;NK2受体的mRNA和蛋白的表达量在应激后大鼠的下丘脑中明显升高,经氟西汀干预后可恢复到正常水平,说明NK2受体与抑郁症的发生、发展过程具有相关性,在抑郁症的发病机制中可能发挥重要作用.     

选择性5-羟色胺再摄取抑制剂对小胶质细胞不同活化途径的影响

目的 探讨SSRIs氟西汀和艾司西酞普兰对于小胶质细胞不同活化途径的影响.方法 新生2 dSD大鼠脑组织经洗涤、分离、消化、过筛网、离心等处理,获得原代小胶质细胞.将BV2细胞系组和原代细胞组进一步分亚组如下:空白对照组、M1型模型组、M2型模型组、氟西汀组和艾司西酞普兰组,干预24h后使用实时定量聚合酶链式反应(real-time quantitative polymerase chain reaction,RT-PCR)、酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)和免疫印迹法测定相关炎症指标表达水平.结果 (1)M1型活化:RT-PCR示氟西汀可显著降低脂多糖联合干扰素-γ(LPS+INF-γ)诱导的BV2细胞白细胞介素1β(interleukin 1β,IL-1β)、IL-6、肿瘤坏死因子a(tumor necrosis factor,TNF-a)和诱导型一氧化氮合成酶(inducible nitric oxide synthase,iNOS)mRNA表达(均P＜0.05).氟西汀和艾司西酞普兰均可显著抑制LPS+ INF-γ诱导的原代小胶质细胞IL-6(均P＜0.01)、TNF-a(P =0.018、0.029)和iNOS(均P=0.005)mRNA表达.免疫印迹法示氟西汀和艾司西酞普兰可显著抑制LPS+ INF-γ诱导的BV2细胞Iba-1 (P ＜0.01、P=0.002)、CD86(均P＜0.01)蛋白表达.氟西汀和艾司西酞普兰均可显著抑制LPS+ INF-γ诱导的原代小胶质细胞CD86表达(均P＜0.01).ELISA示氟西汀可显著抑制LPS+ INF-γ诱导的BV2细胞TNF-a(P=0.003)和IL-1 β(P=0.002)分泌.氟西汀和艾司西酞普兰可显著抑制LPS+ INF-γ诱导的原代小胶质细胞IL-1β分泌(均P＜0.01).原代小胶质细胞各组间TNF-a分泌差异无统计学意义(F=4.627,P=0.053),进一步组间比较示与模型组[(11.6±1.1)g/L]相比,艾司西酞普兰组[(20.2±1.9) g/L]TNF-a表达增高(P=0.012).(2)M2型活化:RT-PCR示氟西汀可显著提高IL-4诱导的原代小胶质细胞IL-10 mRNA表达(P=0.036).免疫印迹法示氟西汀可显著提高IL-4诱导的BV2细胞(P=0.016)和原代小胶质细胞(P＜0.01)CD206表达.ELISA示氟西汀可显著提高IL-4诱导的BV2细胞(P=0.044)和原代小胶质细胞(P＜0.01)IL-10分泌.结论 氟西汀和艾司西酞普兰可通过影响小胶质细胞活化状态而发挥免疫调节作用,这可能是SSRI类抗抑郁剂发挥抗抑郁作用机制之一.     

Notch1 signaling,hippocampal neurogenesis and behavioral responses to chronic unpredicted mild stress in adult ischemic rats

Accumulating evidence indicates that the Notch signaling pathway fulfills important roles in ischemia-stimulated neurogenesis, which may be regarded as an etiological factor in post-stroke depression. Here we explored Notch₁ signaling, hippocampal neurogenesis and behavioral responses to chronic unpredicted mild stress (CUMS) in adult ischemic rats. Animals were treated with permanent middle cerebral artery occlusion followed by an 18 day CUMS procedure. Proliferating cells in the hippocampus and their cell fate were investigated on days 19 and 28 after ischemic surgery. Additionally, expression of the Notch₁ intracellular domain (NICD) and its downstream targets Hes1 and Hes5 was examined. A sucrose preference test and forced swim test were used to assess behavioral responses. CUMS produced depressive-like behaviors and decreased the number of proliferating cells on day 19 (both p < 0.001), accompanied by a decreased expression of both Hes1 and Hes5 in the hippocampus of ischemic animals (p < 0.001). On day 28, CUMS resulted in a decreased number of neurogenically-differentiating cells in the subgranular zone (p < 0.001) while permitting differentiation into astrocytes in the hilus (p < 0.05). Hes1 and Hes5 protein expression levels were increased. The expression of the NICD was significantly decreased at both time-points. CUMS led to expression changes in the Notch₁ signaling cascade in ischemic rats, most of which concerned hippocampal neurogenesis. This suggests that variation in Notch₁ activity and subsequent expression of its downstream targets, including Hes1 and Hes5, may, at least in part, contribute to modulation of ischemia-related hippocampal neurogenesis by CUMS.     

重复经颅磁刺激对抑郁模型大鼠行为学及海马区糖皮质激素受体表达的影响

目的观察重复经颅磁刺激(repetitive transcranial magnetic stimulation,r TMS)对慢性应激抑郁模型大鼠的抗抑郁作用及对海马区糖皮质激素受体(glucocorticoid receptor,GR)表达的影响,探讨r TMS抗抑郁作用的可能机制。方法 75只健康成年雄性大鼠随机分为造模组(60只)和空白对照组(15只),造模组采用孤养联合慢性温和不可预见应激(chronic unpredictability stimulus,CUMS)方法制备抑郁大鼠模型,为期3周,筛选造模成功的大鼠45只随机分为r TMS组、伪r TMS组和抑郁对照组,每组15只,r TMS组和伪r TMS组分别接受10 Hz的r TMS刺激和伪刺激干预3周,抑郁对照组和空白对照组不给予干预。分别于造模前、造模后、r TMS干预后进行体重测量、蔗糖水消耗实验和强迫游泳实验评估,r TMS干预后检测大鼠海马区GR蛋白和海马GR m RNA表达水平。结果造模后,r TMS组、伪r TMS组和抑郁对照组大鼠蔗糖水消耗量较空白对照组下降,强迫游泳不动时间增加(P0.01)。r TMS干预后,r TMS组体重增长率、蔗糖水消耗量与伪r TMS组和抑郁对照组相比均较高(P0.01),强迫游泳不动时间较短(P0.01)。伪r TMS组及抑郁对照组海马区GR蛋白及其m RNA表达水平与r TMS组和空白对照组相比均较低(P0.05)。结论 r TMS能够改善CUMS抑郁模型大鼠的抑郁样行为,可能与上调海马区GR表达有关。     

Notch3 signaling promotes radial glial/progenitor character in the mammalian telencephalon

The Notch signaling pathway is known to influence cell fate in the developing mammalian nervous system. Previous work in the mouse telencephalon has shown that activated Notch1 promotes radial glial and astrocytic character in vivo, and fibroblast growth factor (FGF)-responsive neural progenitor character in vitro. In light of studies suggesting that Notch3 can antagonize Notch1, we tested the effects of activated Notch3 (NICD3) in the mouse telencephalon. Infection of embryonic day 9.5 telencephalic progenitors in vivo with NICD3 promoted radial glial/progenitor character embryonically and astrocyte fate postnatally. In addition, expression of NICD3 in telencephalic progenitors in vitro increased neurosphere frequency in FGF2, but was incompatible with neurosphere growth in epidermal growth factor (EGF). Thus, in the developing telencephalon, Notch1 and Notch3 function similarly, and may activate similar signaling cascades. Consistent with this notion, expression of an activated form of the Notch effector CBF1 (CBF1-VP16), or of the pathway target Hes5 promoted radial glial/progenitor character in vivo. Interestingly, unlike NICD1 and NICD3, CBF1-VP16 and Hes5 did not inhibit neurosphere growth in EGF, suggesting that this effect may be mediated at least in part by CBF1/Hes-independent signaling.     

盐酸氟西汀联合利培酮治疗难治性抑郁症的效果及对患者睡眠质量的影响

目的探讨盐酸氟西汀联合利培酮治疗难治性抑郁症临床效果及对患者睡眠质量的影响,为难治性抑郁症的治疗提供参考。方法选取2015年1月-2016年10月就诊于新疆维吾尔自治区人民医院符合《国际疾病分类(第10版)》(ICD-10)诊断标准的92例难治性抑郁症患者,采用随机数字表法分为盐酸氟西汀组(对照组)和盐酸氟西汀联合利培酮组(观察组)各46例,疗程8周。于治疗前和治疗8周后,采用汉密尔顿抑郁量表17项版(HAMD-17)评定疗效,采用匹兹堡睡眠指数量表(PSQI)评定睡眠质量,采用自制不良反应记录表记录药物治疗过程中不良反应发生情况。结果治疗8周后,观察组总有效率高于对照组(93.5%vs.78.3%,χ~2=4.39,P0.05),观察组HAMD-17评分低于对照组[(13.2±2.8)分vs.(16.3±3.4)分,t=4.77,P0.01],PSQI评分较对照组低[(10.2±1.2)分vs.(12.1±1.4)分,t=6.99,P0.01]。两组不良反应发生率比较差异无统计学意义(6.5%vs.13.0%,χ~2=0.49,P=0.48)。结论单用盐酸氟西汀与盐酸氟西汀联合利培酮均可改善难治性抑郁症患者的临床症状及睡眠质量,但联合用药较单用盐酸氟西汀效果更好,二者安全性相当。     

Caveolin-1 regulates neural differentiation of rat bone mesenchymal stem cells into neurons by modulating Notch signaling

Bone marrow mesenchymal stem cells (MSCs) are known to differentiate into neurons in vitro. However, the mechanism underlying MSC differentiation remains controversial. A recent analysis has shown that Notch signaling is involved in regulating the differentiation of MSCs. This study examines the potential mechanism of the differentiation of MSCs into neurons, and it considers the role of caveolin-1 in this process. We investigated neuron differentiation and Notch signaling by detecting the expression levels of microtubule-associated protein 2 (MAP-2), Neuron-specific Enolase (NSE), Notch-1, Notch intracellular domain (NICD) and hairy enhancer of split 5 (Hes5). We found that by down-regulating caveolin-1 during induction, MSCs were prone to neural differentiation and expressed high levels of neuronal markers. Meanwhile, the expression levels of Notch-1, NICD and Hes5 decreased. Our results indicate that down-regulation of caveolin-1 promotes the neuronal differentiation of MSCs by modulating the Notch signaling pathway.