切割穹窿海马伞海马Brn-4 mRNA的表达及NGF对其自体NSCs增殖和向神经元分化的影响
|
摘要
第一部分RT-PCR/Southern杂交法检测穹窿海马伞切割大鼠海马Brn-4 mRNA的表达变化
目的:用RT-PCR/Southern杂交法进一步观察切割穹窿海马伞大鼠海马与正常海马内Brn-4 mRNA表达的差异,探讨穹窿海马伞切割后海马内神经再生与修复的分子生物学机制。方法:42只SD大鼠随机分成7组,每组6只。1组为正常对照组,其余6组分别为切割双侧穹窿海马伞后1、3、7、14、21和28d组。取各组大鼠的海马组织,提取总RNA,采用RT-PCR/Southern杂交方法分析穹窿海马伞切割后海马内Brn-4 mRNA表达水平的变化。以各组Brn-4与内参GAPDH RT-PCR/Southern杂交条带的光密度比值表示Brn-4 mRNA的相对表达量,使用Stata7.0统计学软件进行单因素方差分析和两两比较。结果:海马内Brn-4 mRNA的相对表达量正常组为0.254±0.018,切割后1d、3d、7d、14d、21d、28d组分别为0.277±0.019、0.516±0.014、1.497±0.081、2.357±0.133、1.140±0.054、0.264±0.020。统计学分析表明,切割后l d、28 d组与正常对照组相比,Brn-4 mRNA的相对表达量差异无显著性意义(P>0.05),3 d、7 d、14 d和21d组与正常对照组相比,差异均有显著性意义(P<0.01);比较切割后不同时间组,除1 d组与28 d组间的差异无显著性意义(P>0.05)外,其余各组间的表达差异均有显著性意义(P<0.01或0.05)。结论:切割穹窿海马伞后的海马组织中Brn-4 mRNA表达量自切割后第3d开始明显升高,14d时达到最高水平,以后开始下降,于28d恢复至正常水平。结合本课题组以往的工作,Brn-4 mRNA的升高可能与促进海马内神经干细胞向神经元的分化有关。
第二部分NGF对穹窿海马伞切割后海马自体NSCs增殖和向神经元分化的影响
目的:探讨切割穹窿海马伞及脑室给予神经生长因子(nerve growth factor, NGF)后对大鼠海马自体神经干细胞增殖和分化为神经元的影响。方法:12只SD大鼠,随机分成给药组和对照组,每组6只。两组均切割右侧穹窿海马伞,给药组和对照组切割后即时及第2d、4d向侧脑室分别注射NGF和人工脑脊液,并在术后第3～7d每日经腹腔注射BrdU 2次。于术后28d灌注取脑、冰冻切片,行BrdU/NF-200免疫荧光双标检测。分别拍摄海马齿状回同一视野下BrdU阳性细胞和NF-200阳性细胞的图像,然后应用Spot 4.6图像处理软件进行重叠,并分别计数海马齿状回门区、颗粒下层及颗粒层中BrdU阳性细胞和BrdU/ NF-200双标神经元。数据输入Stata 7.0统计软件,进行两因素的方差分析(2×2析因设计),用q检验(SNK法)进行组间比较。结果:海马齿状回内BrdU阳性细胞数,给药组和对照组切割侧明显多于正常侧,给药组切割侧和正常侧分别多于对照组切割侧和正常侧;海马齿状回内的BrdU/NF-200双标神经元数,给药组切割侧最多,给药组正常侧和对照组切割侧较少,而对照组正常侧中则无。结论:切割穹窿海马伞后,可致大鼠海马齿状回中自体神经干细胞增殖加快并向神经元分化。切割穹窿海马伞后于侧脑室中施加NGF,可促进大鼠海马齿状回中自体神经干细胞的增殖和向神经元分化。
PartⅠUsing RT-PCR/Southern Blot to Detect the Change of Brn-4 mRNA Expression in Rat Hippocampus after Fimbria Fornix Transection
Objective: Using RT-PCR/Southern blot to observe the diference of Brn-4 mRNA expression between the fimbria fornix transected rats’hippocampus and the normal ones, to investigate the molecular mechanisms of nerve regeneration and repaire in hippocampus after fimbria fornix transection. Methods: Forty-two SD rats were randomly divided into 7 groups, 6 rats in each group. One group served as normal control and the others served as the 1st, 3rd, 7th, 14th, 21st and 28th day group after fimbria fornix transection, respectively. Then hippocampi were isolated and total RNA was extracted. RT-PCR/Southern blot was used to detect the change of Brn-4 mRNA expression in hippocampus after fimbria fornix transection. The relative expression level of Brn-4 mRNA was indicated by the ratio of the optical density value of Brn-4 hybridization bands to that of reference gene GAPDH. Single factor analysis of variance and multiple comparison was performed using Stata7.0 statistical software. Results: The relative expression level of Brn-4 mRNA in normal group was 0.254±0.018, and in the 1st, 3rd, 7th, 14th, 21st and 28th day group after transection was 0.277±0.019, 0.516±0.014, 1.497±0.081, 2.357±0.133, 1.140±0.054 and 0.264±0.020, respectively. Statistical analysis showed that there were no statistically significant differences between the normal control group and the 1st, 28th day group after transection(P>0.05), there were statistically significant differences between the normal control group and the 3rd, 7th, 14th, 21st day group after transection(P<0.01); there were statistically significant difference between each two groups (P<0.01 or 0.05) except between 1d group and 28d group(P>0.05), compared different time groups after transection. Conclusion: The expression level of Brn-4 mRNA started to increase on the 3rd days after fimbria fornix transection, the peak appeared on the 14th days, then decreased slowly to pre-transection level on the 28th days. Combined with our groups’s previous research data, the expression of Brn-4 mRNA increased after fimbria fornix transection, perhaps, might be related to the neural stem cells diferentiating into neurons in hippocampus.
PartⅡThe Effects of NGF on the Proliferation and Differentiation of Endogenous NSCs in the Hippocampus into Neurons after Fimbria Fornix Transection
Objective: To study the effects of fimbria fornix transection and intraventricular injection of nerve growth factor (NGF) on the proliferation and differentiation of endogenous neural stem cells (NSCs) in the hippocampus into neurons. Methods: Twelve SD rats were divided into the treatment group and control group randomly, six rats in each group. The right fimbria fornix of rats were transected. NGF and artificial cerebrospinal fluid was injected into the lateral ventricle of rats in the treatment group and control group respectively immediately and on the 2nd and 4th day after transection. Bromodeoxyuridin (BrdU) was injected intraperitoneally twice per day from 3 to 7 days after operation. On the 28th day after operation, the brains were perfused for fixation and frozen section. BrdU/NF-200 double-label immunofluorescence was used to detect the proliferatiation and differentiatiation of NSCs into neurons. The pictures of BrdU positive cells and NF-200 positive cells in the same visual field in dentate gyrus were taken, respectively. Then the Spot 4.6 image processing software was used to make pictures overlap, and the numbers of BrdU positive cells and BrdU/NF-200 double labeled cells in dentate gyrus, subgranular zone and granular layer were counted, respectively. Using Stata7.0 statistical software, the data were analyzed with the 2-factors variance analysis(2×2 factorial design), and the q test (SNK) was used for comparison among groups. Results: In dentate gyrus, the number of BrdU positive cells in the transection side were much more than those of normal side both in the treatment group and the control group, and the BrdU positive cells in treatment group were more than those of control group both in the transection side and normal side; The number of BrdU/NF-200 double labeled neurons was the most in the transection side of the treatment group, less in normal side of treatment group and transection side of the control group, but absent in the normal side of the control group. Conclusion: Fimbria fornix transection could cause endogenous neural stem cells in the hippocampus proliferate and differentiate into neurons, and intraventricular injection of NGF could facilitate its proliferation and differentiation of endogenous NSCs in the hippocampus into neurons.
目的:用RT-PCR/Southern杂交法进一步观察切割穹窿海马伞大鼠海马与正常海马内Brn-4 mRNA表达的差异,探讨穹窿海马伞切割后海马内神经再生与修复的分子生物学机制。方法:42只SD大鼠随机分成7组,每组6只。1组为正常对照组,其余6组分别为切割双侧穹窿海马伞后1、3、7、14、21和28d组。取各组大鼠的海马组织,提取总RNA,采用RT-PCR/Southern杂交方法分析穹窿海马伞切割后海马内Brn-4 mRNA表达水平的变化。以各组Brn-4与内参GAPDH RT-PCR/Southern杂交条带的光密度比值表示Brn-4 mRNA的相对表达量,使用Stata7.0统计学软件进行单因素方差分析和两两比较。结果:海马内Brn-4 mRNA的相对表达量正常组为0.254±0.018,切割后1d、3d、7d、14d、21d、28d组分别为0.277±0.019、0.516±0.014、1.497±0.081、2.357±0.133、1.140±0.054、0.264±0.020。统计学分析表明,切割后l d、28 d组与正常对照组相比,Brn-4 mRNA的相对表达量差异无显著性意义(P>0.05),3 d、7 d、14 d和21d组与正常对照组相比,差异均有显著性意义(P<0.01);比较切割后不同时间组,除1 d组与28 d组间的差异无显著性意义(P>0.05)外,其余各组间的表达差异均有显著性意义(P<0.01或0.05)。结论:切割穹窿海马伞后的海马组织中Brn-4 mRNA表达量自切割后第3d开始明显升高,14d时达到最高水平,以后开始下降,于28d恢复至正常水平。结合本课题组以往的工作,Brn-4 mRNA的升高可能与促进海马内神经干细胞向神经元的分化有关。
第二部分NGF对穹窿海马伞切割后海马自体NSCs增殖和向神经元分化的影响
目的:探讨切割穹窿海马伞及脑室给予神经生长因子(nerve growth factor, NGF)后对大鼠海马自体神经干细胞增殖和分化为神经元的影响。方法:12只SD大鼠,随机分成给药组和对照组,每组6只。两组均切割右侧穹窿海马伞,给药组和对照组切割后即时及第2d、4d向侧脑室分别注射NGF和人工脑脊液,并在术后第3～7d每日经腹腔注射BrdU 2次。于术后28d灌注取脑、冰冻切片,行BrdU/NF-200免疫荧光双标检测。分别拍摄海马齿状回同一视野下BrdU阳性细胞和NF-200阳性细胞的图像,然后应用Spot 4.6图像处理软件进行重叠,并分别计数海马齿状回门区、颗粒下层及颗粒层中BrdU阳性细胞和BrdU/ NF-200双标神经元。数据输入Stata 7.0统计软件,进行两因素的方差分析(2×2析因设计),用q检验(SNK法)进行组间比较。结果:海马齿状回内BrdU阳性细胞数,给药组和对照组切割侧明显多于正常侧,给药组切割侧和正常侧分别多于对照组切割侧和正常侧;海马齿状回内的BrdU/NF-200双标神经元数,给药组切割侧最多,给药组正常侧和对照组切割侧较少,而对照组正常侧中则无。结论:切割穹窿海马伞后,可致大鼠海马齿状回中自体神经干细胞增殖加快并向神经元分化。切割穹窿海马伞后于侧脑室中施加NGF,可促进大鼠海马齿状回中自体神经干细胞的增殖和向神经元分化。
PartⅠUsing RT-PCR/Southern Blot to Detect the Change of Brn-4 mRNA Expression in Rat Hippocampus after Fimbria Fornix Transection
Objective: Using RT-PCR/Southern blot to observe the diference of Brn-4 mRNA expression between the fimbria fornix transected rats’hippocampus and the normal ones, to investigate the molecular mechanisms of nerve regeneration and repaire in hippocampus after fimbria fornix transection. Methods: Forty-two SD rats were randomly divided into 7 groups, 6 rats in each group. One group served as normal control and the others served as the 1st, 3rd, 7th, 14th, 21st and 28th day group after fimbria fornix transection, respectively. Then hippocampi were isolated and total RNA was extracted. RT-PCR/Southern blot was used to detect the change of Brn-4 mRNA expression in hippocampus after fimbria fornix transection. The relative expression level of Brn-4 mRNA was indicated by the ratio of the optical density value of Brn-4 hybridization bands to that of reference gene GAPDH. Single factor analysis of variance and multiple comparison was performed using Stata7.0 statistical software. Results: The relative expression level of Brn-4 mRNA in normal group was 0.254±0.018, and in the 1st, 3rd, 7th, 14th, 21st and 28th day group after transection was 0.277±0.019, 0.516±0.014, 1.497±0.081, 2.357±0.133, 1.140±0.054 and 0.264±0.020, respectively. Statistical analysis showed that there were no statistically significant differences between the normal control group and the 1st, 28th day group after transection(P>0.05), there were statistically significant differences between the normal control group and the 3rd, 7th, 14th, 21st day group after transection(P<0.01); there were statistically significant difference between each two groups (P<0.01 or 0.05) except between 1d group and 28d group(P>0.05), compared different time groups after transection. Conclusion: The expression level of Brn-4 mRNA started to increase on the 3rd days after fimbria fornix transection, the peak appeared on the 14th days, then decreased slowly to pre-transection level on the 28th days. Combined with our groups’s previous research data, the expression of Brn-4 mRNA increased after fimbria fornix transection, perhaps, might be related to the neural stem cells diferentiating into neurons in hippocampus.
PartⅡThe Effects of NGF on the Proliferation and Differentiation of Endogenous NSCs in the Hippocampus into Neurons after Fimbria Fornix Transection
Objective: To study the effects of fimbria fornix transection and intraventricular injection of nerve growth factor (NGF) on the proliferation and differentiation of endogenous neural stem cells (NSCs) in the hippocampus into neurons. Methods: Twelve SD rats were divided into the treatment group and control group randomly, six rats in each group. The right fimbria fornix of rats were transected. NGF and artificial cerebrospinal fluid was injected into the lateral ventricle of rats in the treatment group and control group respectively immediately and on the 2nd and 4th day after transection. Bromodeoxyuridin (BrdU) was injected intraperitoneally twice per day from 3 to 7 days after operation. On the 28th day after operation, the brains were perfused for fixation and frozen section. BrdU/NF-200 double-label immunofluorescence was used to detect the proliferatiation and differentiatiation of NSCs into neurons. The pictures of BrdU positive cells and NF-200 positive cells in the same visual field in dentate gyrus were taken, respectively. Then the Spot 4.6 image processing software was used to make pictures overlap, and the numbers of BrdU positive cells and BrdU/NF-200 double labeled cells in dentate gyrus, subgranular zone and granular layer were counted, respectively. Using Stata7.0 statistical software, the data were analyzed with the 2-factors variance analysis(2×2 factorial design), and the q test (SNK) was used for comparison among groups. Results: In dentate gyrus, the number of BrdU positive cells in the transection side were much more than those of normal side both in the treatment group and the control group, and the BrdU positive cells in treatment group were more than those of control group both in the transection side and normal side; The number of BrdU/NF-200 double labeled neurons was the most in the transection side of the treatment group, less in normal side of treatment group and transection side of the control group, but absent in the normal side of the control group. Conclusion: Fimbria fornix transection could cause endogenous neural stem cells in the hippocampus proliferate and differentiate into neurons, and intraventricular injection of NGF could facilitate its proliferation and differentiation of endogenous NSCs in the hippocampus into neurons.
引文
1. Baizabal JM, Furlan-Magaril M, Santa-Dlalla J, et al. Neural stem cells in development and regenerative medicine. Arch Med Res, 2003, 34 (6):572-588.
2. Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science, 1992, 255(5052):1707-1710.
3. Richards LJ, Kilpatrick TJ, Bartlett PF. De novo generation of neuronal cells from the adult mouse brain. Proc Natl Acad Sci USA, 1992, 89(18):8591-8595.
4. Roisen FJ, Klueber KM, Lu CL, et al. Adult human olfactory stem cells. Brain Res, 2001, 890(1):11-22.
5. Roy NS, Wang S, Jing L, et al. In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus. Nat Med, 2000, 6(3):271-277.
6. Akamatsu W, Okano H. Neural stem cell, as a source of graft material for transplantation in neuronal disease. No To Hattatsu, 2001,33(2):114-120.
7. Dutton R, Bartlett PF. Precursor cells in the subventricular zone of the adult mouse are actively inhibited from differentiating into neurons. Dev Neurosci, 2000,22(1-2):96-105.
8. Fjose A, McGinnis WJ, Gehring WJ. Isolation of a homoeobox-containing gene from the engrailed region of Drosophila and the spatial distribution of its transcripts. Nature, 1985, 313(6000): 284-289.
9. Li P, He X, Gerrero MR, et al. Spacing and orientation of bipartite DNA-binding motifs as potential functional determinants for POU domain factors. Genes Dev, 1993, 7(12B):2483-2496.
10.徐慧君主编。神经生物学。苏州:苏州大学出版社.。2004, 113-115.
11. Ma Y, Certel K, Gao Y, et al. Functional inetractions between drosophilia bHLH/PAS, sox, and POU transeription factors regulate CNS middline expression of the slit gene. J Neurosci, 2000, 20(12):4596-4605.
12. Sobol SE, Teng X, Crenshaw EB 3rd. Abnormal mesenchymal differentiation in the supperior semicircular canal of Brn-4/pou3f4 knockout mice. Arch Otolaryngol Head Neck Surg, 2005,131(1):41-45.
13. Samadi DS, Saunders JC, Crenshaw EB 3rd, et al. Mutation of the POU-domain gene Brn-4/Pou3f4 affects middle-ear sound conduction in the mouse. Hear Res, 2005,199(1-2):11-21.
14. Josephson R,Muller T,Pickel J, et al. POU transcription factors control expression of CNS stem cell-specific genes. Development,1998, 125(16):3087-3100.
15. Shimazaki T, Arseni jevic Y, Ryan AK, et al. A role for the POU-Ⅲtranscription factor Brn-4 in the regulation of striatal neuron precursor differentiation. EMBO J, 1999,18(2):444-456.
16. Monuki ES, Kuhn R, Weinmaster G, et al. Expression and activity of the POU transcription factor SCIP. Science, 1990, 249 (4974): 1300-1303.
17. Jaegle M, Mandemakers W, Broos L, et al. The POU factor Oct-6 and Schwann cell differentiation. Science, 1996, 273(5274):507-510.
18. Mathis JM, Simmons DM, He X, et al. Brain 4: a novel mammalian POU domain transcription factor exhibiting restricted brain-specific expression. EMBO J, 1992, 11(7):2551-2561.
19.王磊,金国华,秦建兵,等。穹窿海马伞切割大鼠海马内Brn-4 mRNA的表达变化。解剖学报, 2006, 37(4):387-390.
20.王磊,金国华,秦建兵,等。切割穹窿海马伞大鼠海马内Brn-4 mRNA的表达变化—原位杂交法。解剖学报, 2007, 38(4):385-389.
21.方秀斌主编。神经肽与神经营养因子。北京:人民卫生出版社, 2002,283-287.
22. Weskamp G,Gasser UE, Dravid AR, et al. Fimbria-fornix lesion increases nerve growth factor content in adult rat septum and hippocampus. Neurosci Lett, 1986, 70(1):121-126.
23. Larkfors L, Stromberg I, Ebendal T, et al. Nerve growth factor protein level increases in the adult rat hippocampus after a specific cholinergic lesion. J Neurosci Res, 1987, 18(4):525-531.
24. Cellerino A. Expression of messenger RNA coding for the nerve growth factor receptor trkA in the hippocampus of the adult rat. Neuroscience, 1996, 70(3):613-616.
25.金国华,张新化,田美玲,等。大鼠海马内移植神经干细胞的存活和迁移.神经解剖学杂志, 2003, 19(4):378-382.
26.张新化,金国华,秦建兵,等。穹窿海马伞切割侧海马对植入神经干细胞分化为神经元的影响.神经解剖学杂志, 2004, 20(4): 360-364.
27.金国华,张新化,田美玲,等。穹窿海马伞切割侧海马提取液对神经干细胞分化为神经元的促进作用。解剖学报,2004, 40(2):141-145.
28. Price J, Williams BP. Neural stem cells. Curr opin Neurobiol, 2001, l1(5):564-567.
29. Gage FH . Mammalian neural stem cells . Science, 2000 ,287(5457):1433-1438.
30. Riddibough G. Developmental biology. Homing in on the homeobox. Nature, 1992, 357(6380): 643-644.
31. Andersen B, Resenfeld MG. POU domain factors in the neuroendocrine system: lessons from developmental biology provide insights into human disease. Endocr Rev, 2001, 22(1):2-35.
32. Hobert O, Westphal H. Functions of LIM-homecbox genes.Trends Genet, 2000, 16(2):75-83.
33. Le Moine C, Young WS. RHS2, A POU domain-containing gene,and its expression in developing and adult rat. Proc Natl Acad Sci USA, 1992, 89(8):3285-3289.
34. Munoz JR, Stoutenger BR, Robinson AP, et al. Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice. Proc Natl Acad Sci USA,2005,102(50):18171-18176.
35. Bovetti S, Bovolin P, Perroteau I , et al. Subventricular zone-derived neuroblast migration to the olfactory bulb is modulated by matrix remodelling. Neuroscience,2007,25(7):2021-2033.
36. McDonald HY,Wojtowiez JM. Dynamics of neurogenesis in the dentate gyrus of adult rats.Neurosci Lett,2005,385(1):70-75.
37. Sugaya K. Neuroreplacement therapy and stem cell biology under disease conditions. Cell Mol Life Sci,2003,60(9):1891-1902.
38.徐慧君。神经生物学。苏州大学出版社,2004:143-158.
39.龙大宏,杨丹迪,李佳楣,等。穹窿海马伞损伤对大鼠学习记忆海马GFAP阳性神经胶质细胞的影响。神经解剖学杂志, 2002, 18 (1) : 63-66.
40. Wu H, Friedman WJ, Dreyfus CF,et a1. Differential regulation of neurotrophin expression in basal forebrain astrocytes by neuronal signals.Neurosci Res,2004,76(1):76-85.
41. Murer MG, Yan Q, Raisman-Vozari R, et a1. Brain-derived neurotrophic factor in the control human brain,and in Alzhelmer’s disease and Parkinson’s disease. Progress in Neurobiology, 2001, 63(1):71-124.
42. Cattaneo E, Mckey R. Proliferation and differentiation of neuronal stem cells regulated by nerve growth factor. Nature, 1990, 347:762- 765.
43. Alderson RF, Alterman AL, Barde YA, et al. Brain-derived neurotrophic factor increases survival and differentiated functions ofrat septal cholinergic neurons in culture. Neuron, 1990, 5(3):297-306.
44.金国华,陈蓉,田美玲,等。海马中56 kD蛋白诱导人神经干细胞向神经元分化的作用。神经解剖学杂志, 2006, 22(4): 389-393.
45. Toncher AB, Yamashima T. Differential neurogenic potential of progenitor cells in dentate gyrus and CA1 sector of the postischemic adult monkey hippocampus. Exp neurol, 2006, 198(1):101-113.
46. Lichtenwalner KJ, Parent JM. Adult neurogenesis and the ischemic forebrain. J Cereb Blood Flow Metab, 2006, 26(1):1-20.
47. Calza L, Giuliani A, Fernandez M, et al. Neural stem cells and cholinergic neurons: Regulation byimmunolesion and treatment with mitogens, retinoic acid, and nerve growth factor. Proc Natl Acad Sci USA, 2003, 100(12):7325-7330.
1. Kaplan DR and Miller FD. Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol, 2000, 10(3): 381-391.
2. Blusztajn JK, Berse B. The cholinergic neuronal phenotype in Alzheimer’S disease. Metabolic Brain Disease, 2000, 15(1):45-64.
3.朱长庚。神经解剖学。北京:人民卫生出版社,2002, 266-268.
4. Rao ZR,Yamano M,Wanaka A,et al. Distribution of cholinergic neurons and fibers in the hypothalamus of the rat using choline acetyltransferase as a marker. Neuroscience, 1987, 20(3): 923-934.
5. Mesulam MM,Avoli M,Reader TA, et al. Central Cholinergic Pathways:Neuroanatomy and some behavioral implications. Neurotransmitters and Cortical Function, 1988, 237-260.
6. Oh JD ,Woolf NJ ,Roghania A, et al. Cholinergic neurons in the rat central nervous system demonstrated by in situ hybridization of choline acetyltransferase mRNA. Neuroscience, 1992, 47(4):807-822.
7. Kasashima S, Muroishi Y, Futakuchi H, et al. In situ mRNA hybridization study of the distribution of choline acetyltransferase in the human brain.Brain Res, 1998, 806(1):8-15.
8.许绍芬。神经生物学。上海:上海医科大学出版社,1999, 142-144.
9. Armstrong DM, Saper CB, Levy AI, et al. Distribution of Cholinergic Neurons in the rat Brain:Demonstrated by the Immunocytomical Localization of Choline Acetyltransferase. J Comp Neurol, 1983, 216(1):53-68.
10. Muir JL. Acetylcholine , aging , and Alzheimer’s disease.Pharmacol Biochem Behav, 1997, 56:687-696.
11. Houser CR, Crawford GD, Salvaterra PM, et al. Immunocytochemical Localization of Choline Acetyltransferase in Rat Cerebral Cortex:A Study of Cholinergic Neurons and Synapses.J Comp Neurol, 1985,234(1):17-34.
12. Cowan WM,Viktor Hamburger, Rita Levi-Montalcin.The path to the discovery of nerve growth factor.Annu Rev Neurosci, 2001, 24: 551-600.
13. Barde YA , Edger D , Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO J, 1982, 1(5):549-553.
14. Leibrock J , Lottspeich H , Hohn A,et al .Molecular cloning and expression of brain derived neurotrophic factor. Nature, 1989, 341(6238):149-152.
15. Wang JM, Zeng YS, Liu RY, et al. Recombinant adenovirus vector -mediated functional expression of neurotropin-3 receptor (TrkC) in neural stem cells. Exp Neurol, 2007, 203 (1):123-127.
16. Ducray A, Kipfer S, Huber AW, et al. Creatine and neurotrophin-4/5 promote survival of nitric oxide synthase - expressing interneurons in striatal cultures. Neurosci Lett, 2006, 395 (1):57 - 62.
17. Berkemeier LR,Ozcelik T, Francke U, et al . Human chromosome 19 contains the neurotrophin-5 gene locus and three related genes that may encode novel acidic neurotrophins . J Somat Cell Mol, 1992, 18(3): 233-245.
18. Li X , Lottspeich F , Gotz R. Recombinant fish neurotrophin-6 is a heparin-binding glycoprotein: implications for a role in axonal guidance. J Biochem ,1997, 324(2):461-466.
19. Nilsson AS, Fainzilber M, Falck P, et al. Neurotrophin-7: a novel member of the neurotrophin family from the zebrafish. FEBS Letters, 1998, 424(3): 285-290.
20. Chao MV. Neurotroph receptors: A window into neuronal differentiation. Neuron, 1992, 9(4):583-593.
21. Kaplan DR, Hempstead BL Marti-Zanca D, et al. The trk proto-oncogene product a signal transducing receptor for nervegrowth factor. Science, 1991, 252(5005):554-558.
22. Ringstedt T, Lagercrantz H and Persson H. Expression of members of the trk family in the developing postnatal rat brain. Brain Res Dev Brain Res, 1993, 72(1):119-131.
23. Lamballe F , Klein R , Barbacid M. TrkC , a new member of the trk family of tyrosine protein kinase , is a receptor for neurotrophin-3. Cell, 1991, 66(5):967-979.
24. Rodrigues-Tebar A, Dechant G and Barde YA. Binding of brain-derived neurotrophic factor to the nerve grow th factor receptor. Neuron, 1990, 4:487-492.
25.蔡文琴,李海标。发育神经生物学。北京:科学出版社,1999,325-327.
26. Wu H, Friedman WJ, Dreyfus CF,et a1. Differential regulation of neurotrophin expression in basal forebrain astrocytes by neuronal signals. Neurosci Res, 2004, 76(1):76-85.
27. Murer MG, Yan Q, Raisman-Vozari R, et a1. Brain-derived neurotrophic factor in the control human brain,and in Alzhelmer’s disease and Parkinson’s disease. Progress in Neurobiology, 2001, 63(1):71-124.
28. Cattaneo E, Mckey R. Proliferation and differentiation of neuronal stem cells regulated by nerve growth factor[J ]. Nature, 1990, 347: 762-765.
29. Ibanez CF. Structure-function relationships in the neurotrophin family. J Neurobiol, 1994, 25(11):1349-1361.
30. Salehi A, Delcroix JD, Swaab DF. Alzheimer’s disease and NGF signaling. J Neural Transm. 2004, 111(3):323-345.
31. Albeck D, Mesches MH, Juthbery S, et al. Exogenous NGF restores endogenous NGF distribution in the brain of the cognitively impaired aged rat. Brain Res, 2003, 967(1-2):306-3l0.
32. Crouley C, Spencer SD, Nishimura MC, et al. Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain chlinergic neurons. Cell, 1994, 76 (16):1001- 1011.
33. Macphee I, Barker PA. Extended ceramide exposure activates the TrkA receptor by increasing receptor homodimer formation. J Neurochem, 1999, 72(4):1423-1430.
34. Kaplan DR, Miller FD. Signal transduction by the neutrophin receptors. Curr Opin Cell Biol, 1997, 9(2):213-221.
35. Holtzman DM, Kilbridge JO, L i YW, et al. TrkA expression in the CNS: evidence for the existence of several novel NGF-responsive CNS neurons. J Neurosci, 1995, 15(2):1567-1576.
36. Gibbs RB, Pfaff DW. In situ hybridization detection of TrkA mRNA in brain: distribution co localization w ith p75NGFR and up regulation by nerve grow th factor. J Comp Neurol, 1994, 341(3):324-339.
37.蔡维君,邓小华,罗学港。大鼠Meynert基底核TrkA和ChAT的表达.神经解剖学杂志,2000, 16(3):234-238.
38. German DC, Yazdani U, Speciale SG, etal. Cholinergic neuropathology in a mouse model of Alzheimer’s disease. J Comp Neurol, 2003, 462(4):371-381.
39. Large TH, Bodary SC, Clegg DO, et al. Nerve growth factor gene expression in the developing rat brain. Science, 1986, 234(4774): 352-355.
40.王永忠,张志坚,刘锦波,姜平,查小英。神经生长因子受体TrkA在新生鼠、幼鼠及成鼠脊髓表达差异的研究。神经解剖学杂志,2002, 18(4):361-362.
41. Altar CA, Cai N, Bliven T, et al. Anterograde transport of brain-derived neurotrophic factor and its role in the brain. Nature, 1997, 389(6653):856-860.
42. Mertz K, Koscheck T, Schilling K. Brain derived neurotrophic factor modulates dend ritic morphology of cerebellar basket and stellate cells:Aninviron study. Neur Science, 2000, 97(2):303-310.
43. Knusel B, Winslow JW, Rosenthal A, et al. Promotion of central cholinergic and dopaminergic neuron differentiation by brain- derived neurotrophic factor but not neurotrophin 3. Proc Natl Acad Sci USA , 1991, 88(3):961-965.
44. Lindsay RM, Wiegand SJ, Altar CA, et al. Neurotrophic factors: from molecule to man. Trends Neurosci, 1994, 17(5):182-190.
45. Alderson RF, Alterman AL, Barde YA, et al. Brain-derived neurotrophic factor increases survival and differentiated functions of rat septal cholinergic neurons in culture. Neuron, 1990, 5(1): 297-306.
46. Martinez-Serrano A, Hantzopoulos PA, Bjorklund A. Ex vivo gene transfer of brain-derived neurotrophic factor to the intact rat forebrain: neurotrophic effects on cholinergic neurons. Eur J Neurosci, 1996, 8(4): 727-735.
47.金国华,徐慧君,武义鸣,等。BDNF、NGF对体外培养的胚胆碱能神经元生长发育的影响。神经解剖学杂志,1997, 13(3):230-234.
48.金国华,徐慧君,武义鸣,等。BDNF、NGF对AD模型鼠脑移植区胚胆碱能神经元发育生长的调控。解剖学报,1999, 30(2):107-112.
49.金国华,田美玲,秦建兵,等。BDNF、NGF对体外长期培养的胚基底前脑胆碱能神经元的影响。神经解剖学杂志,2001, 17(4): 337-341.
50. NonnerD, Barrett JN. Changes in the response of cultured septal cholinergic neurons to nerve growth factor exposure and deprivation during the first postnatal month. Dev Brain Res,1994, 79(2):219- 228.
51. Morse JK, Wiegand SJ, Anderson K, et al. Brain-derived neurotrophic factor (BDNF) prevents the degeneration of medial septal cholinergic neurons following fimbria transection. J Neurosci, 1993, 13 (10):4146 -4156.
52. Iskandrian AS. Adenosine myocardial perfusion imaging. J Nucl Med, 1994, 35(4):734-736.
53. Emfors P. Identification of cells in rat brain and peripheral tissues expressing mRNA for members of the nerve growth factor family. Neuron, 1990, 5(4):511-526.
54. Maisonpierre PC, Belluscio L, Squinto S, et al. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science, 1990, 247(4949): 1446-1451.
55. Novikoval LN, Novikov LN, Kellerth JO. Survival effects of BDNF and NT- 3 on axotomized rubrospinal neurons depend on the temporal pattern of neurotrophin administration. Eur J Neurosci, 2000, 12 (2): 776-780.
56. Zhou XF, Rush RA. Localization of neurotrophin-3-like immunoreactivity in the rat central nervous system. Brain Res, 1994, 643(1-2):162-172.
57. Ip NY, Li Y, Yancopoulos GD, et al. Cultured hippocampal neurons show responses to BDNF, NT-3, and NT-4, but not NGF. J Neurosci, 1993, 13(8):3394-3405.
58. Friedman WJ, Ibanez CF, Hallbook F, et al. Differential actions of neurotrophins in the locus coeruleus and basal forebrain. Exp Neurol, 1993, 119(1):72-78.
59. Lamballe F, Klein R, Barbacid M. TrkC, a new member of the trk family of tyrosine protein kinase, is a receptor for neurotrophin-3. Cell, 1991, 66(5):967-979.
60.刘洁,方秀斌,神经营养因子4/ 5的研究进展。解剖科学进展,2001, 7(3):253-256.
61. Thoenen H. Neurotrophins and neuronal plasticity. Science, 1995, 270(5236):593-598.
62. Stitt NY. Similarities and differences in the way neurotrophins interact with the Trk receptors in neuronal and nonneuronal cells. Neuron, 1993, 10:137-149.
63. Hyman C, J uhasz M. Comparision of the effects of BDNF, NT-3, and NT-4 on dopaminergic and GABAergic neurons of the ventral mesencephalon. J Neurosci, 1994, 14(1):335-347.
64. Ardelt AA, Flaris N, Roth KA. Neurotrophin-4 selectively promotes survival of striatal neurons in organotypic slice culture.Brain Res, 1994, 647(2):340-344.
65. Gtz R, Kster R, Winkler C, et al. Neurotrophin-6 is a new member of the nerve growth factor family. Nature, 1994, 372(6503):266-269.
66. Lai Ko, Fu WY, Ip FC, et al. Cloning and expression of a novel neurotrophin, NT - 7, from carp. Mol Cell Neurosci, 1998, 11 (1-2): 64-76.
67. Wu H, Friedman WJ, Dreyfus CF, et a1. Differential regulation of neurotrophin expression in basal forebrain astrocytes by neuronal signals. Neurosci Res, 2004, 76(1):76-85.
68. Murer MG, Yan Q, Raisman-Vozari R, et a1. Brain-derived neurotrophic factor in the control human brain. and in Alzhelmer’s disease and Parkinson’s disease.Prog Neurobiology, 2001, 63(1): 71-124.
69. Connor B, Dragunow M. The role of neuronal growth factors in neurodegenerative disorders of the human brain. Brain Res Rev, 1998, 27(1):1-39.
70.肖世富,赵瑛,夏斌,等。老年神经精神病学。上海:第二军医大学出版社,2004, 382.
71. Klein RL, Muir D, King MA, et al. Long term action of vector-derived nerve growth factor or brain-derived neurotrophic factor on choline acetyltransferase and trk receptor levels in the adultrat basal forebrain. Neuroscience, 1999, 90(3 ):815-821.
72. Forander P, Soderstrom S, Humpel C, et al. Chronic infusion of nerve growth factor into rat striatum increases cholinergic markers and inhibits striatal neuronal discharge rate. Eur J Neurosci, 1996, 8(9): 1822-1832.
73. Verani MS. Dobutamine myocardial perfusion imaging. J Nucl Med, 1994, 35(4):737-739.
74.龙大宏,姚志彬,李沃棠,等。神经生长因子对老年痴呆鼠学习记忆能力的影响。中国临床康复,2004, 8(10):1951-1953.
75.尹元琴,任常山,陈红,等。阿尔茨海默病模型建立及神经生长因子对ChAT的影响。中国老年学杂志,2004, 24(9):829-831.
76. Swaab DF. Reactivation of atrophic neurons in A1zheimer’s disease. Neurol Res, 2003, 25(6):652-660.
77. Lab SP, Neet KE, Mufson EJ. Nerve growth factor: Structure, function and therapeutic amplications for AIzheimeit’s disease. Curr Drug Target CNS Neurol Disord, 2003, 2(5):315-334.
78. Williams LR, Varon S, Peterson GM,et al. Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria fornix transection. Proc Natl Acad Sci USA, 1986, 83(23): 9231-9235.
79. Verani MS. Dobutamine myocardial perfusion imaging. J Nucl Med, 1994, 35(4):737-739.
80. Eriksdotter JM, Nordberg A, Amberla K, et al. Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer’s disease. Dement Geriatr Cogn Disord, 1998, 9(5):246-257.
81. HE Yunshao, Yao Zhibin, Chen Yici. Effect of nerve growth factor on the lesioned septohippocampal cholinergic system of aged rats. Brain Res, 1991, 552(1):159-163.
82. Tuszynski MH, Roberts J, Senut MC, et al. Gene therapy in the adultprimate brain: intraparenchymal grafts of cells genetically modified to produce nerve growth factor prevent cholinergic neuronal degeneration. Gene Ther, 1996, 3(4):305-314.
83. Calza L, Giuliani A, Fernandez M, et al. Neural stem cells and cholinergic neurons: Regulation byimmunolesion and treatment with mitogens, retinoic acid, and nerve growth factor. Proc Natl Acad Sci USA, 2003, 100(12):7325-7330.
84. Connor B, Yang D, Yan Q, et a1. Brain-derived neurotrophic factor is reduced in Alzhelmer’s disease. Brain Res Mol, 1997, 49(1-2):71-81.
85. Narisawa-saito M, Wakabayashi K, Tsuji S, et a1. Regimral specificity of alterations jn NGF, BDNF and NT-3 levels in Alzheimer disease. Neuroreport, 1996, 7(18):2925-2928.
86. Fischer W, Sirevaag A, Wiegand SJ, et a1. Reversal of spatial memory impairments in aged rats by nerve growth factor and neurotrophins 3 and 4/5 but not by brain-derived neurotrophic factor. Proc Nail Acad Sci USA, 1994, 91(18):8607-8611.
87. Schober A, Wolf N, Huber K, et al. TrkB and neurotrophin-4 are important for development and maintenance of sympathetic pregangtionic neurons innervating the adrenal medulla. J Neurosci, 1998, 18(18): 7272- 7284.
88.Becker E, Soler RM, Yuste VJ, et al. Development of survival responsiveness to brain-derived neurotrophic factor, neurotrophin 3 and neurotrophin 4/ 5, but not to nerve growth factor, in culturedmotoneurons from chick embryo spinal cord. J Neurosci, 1998, 18(19):7903-7911.
2. Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science, 1992, 255(5052):1707-1710.
3. Richards LJ, Kilpatrick TJ, Bartlett PF. De novo generation of neuronal cells from the adult mouse brain. Proc Natl Acad Sci USA, 1992, 89(18):8591-8595.
4. Roisen FJ, Klueber KM, Lu CL, et al. Adult human olfactory stem cells. Brain Res, 2001, 890(1):11-22.
5. Roy NS, Wang S, Jing L, et al. In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus. Nat Med, 2000, 6(3):271-277.
6. Akamatsu W, Okano H. Neural stem cell, as a source of graft material for transplantation in neuronal disease. No To Hattatsu, 2001,33(2):114-120.
7. Dutton R, Bartlett PF. Precursor cells in the subventricular zone of the adult mouse are actively inhibited from differentiating into neurons. Dev Neurosci, 2000,22(1-2):96-105.
8. Fjose A, McGinnis WJ, Gehring WJ. Isolation of a homoeobox-containing gene from the engrailed region of Drosophila and the spatial distribution of its transcripts. Nature, 1985, 313(6000): 284-289.
9. Li P, He X, Gerrero MR, et al. Spacing and orientation of bipartite DNA-binding motifs as potential functional determinants for POU domain factors. Genes Dev, 1993, 7(12B):2483-2496.
10.徐慧君主编。神经生物学。苏州:苏州大学出版社.。2004, 113-115.
11. Ma Y, Certel K, Gao Y, et al. Functional inetractions between drosophilia bHLH/PAS, sox, and POU transeription factors regulate CNS middline expression of the slit gene. J Neurosci, 2000, 20(12):4596-4605.
12. Sobol SE, Teng X, Crenshaw EB 3rd. Abnormal mesenchymal differentiation in the supperior semicircular canal of Brn-4/pou3f4 knockout mice. Arch Otolaryngol Head Neck Surg, 2005,131(1):41-45.
13. Samadi DS, Saunders JC, Crenshaw EB 3rd, et al. Mutation of the POU-domain gene Brn-4/Pou3f4 affects middle-ear sound conduction in the mouse. Hear Res, 2005,199(1-2):11-21.
14. Josephson R,Muller T,Pickel J, et al. POU transcription factors control expression of CNS stem cell-specific genes. Development,1998, 125(16):3087-3100.
15. Shimazaki T, Arseni jevic Y, Ryan AK, et al. A role for the POU-Ⅲtranscription factor Brn-4 in the regulation of striatal neuron precursor differentiation. EMBO J, 1999,18(2):444-456.
16. Monuki ES, Kuhn R, Weinmaster G, et al. Expression and activity of the POU transcription factor SCIP. Science, 1990, 249 (4974): 1300-1303.
17. Jaegle M, Mandemakers W, Broos L, et al. The POU factor Oct-6 and Schwann cell differentiation. Science, 1996, 273(5274):507-510.
18. Mathis JM, Simmons DM, He X, et al. Brain 4: a novel mammalian POU domain transcription factor exhibiting restricted brain-specific expression. EMBO J, 1992, 11(7):2551-2561.
19.王磊,金国华,秦建兵,等。穹窿海马伞切割大鼠海马内Brn-4 mRNA的表达变化。解剖学报, 2006, 37(4):387-390.
20.王磊,金国华,秦建兵,等。切割穹窿海马伞大鼠海马内Brn-4 mRNA的表达变化—原位杂交法。解剖学报, 2007, 38(4):385-389.
21.方秀斌主编。神经肽与神经营养因子。北京:人民卫生出版社, 2002,283-287.
22. Weskamp G,Gasser UE, Dravid AR, et al. Fimbria-fornix lesion increases nerve growth factor content in adult rat septum and hippocampus. Neurosci Lett, 1986, 70(1):121-126.
23. Larkfors L, Stromberg I, Ebendal T, et al. Nerve growth factor protein level increases in the adult rat hippocampus after a specific cholinergic lesion. J Neurosci Res, 1987, 18(4):525-531.
24. Cellerino A. Expression of messenger RNA coding for the nerve growth factor receptor trkA in the hippocampus of the adult rat. Neuroscience, 1996, 70(3):613-616.
25.金国华,张新化,田美玲,等。大鼠海马内移植神经干细胞的存活和迁移.神经解剖学杂志, 2003, 19(4):378-382.
26.张新化,金国华,秦建兵,等。穹窿海马伞切割侧海马对植入神经干细胞分化为神经元的影响.神经解剖学杂志, 2004, 20(4): 360-364.
27.金国华,张新化,田美玲,等。穹窿海马伞切割侧海马提取液对神经干细胞分化为神经元的促进作用。解剖学报,2004, 40(2):141-145.
28. Price J, Williams BP. Neural stem cells. Curr opin Neurobiol, 2001, l1(5):564-567.
29. Gage FH . Mammalian neural stem cells . Science, 2000 ,287(5457):1433-1438.
30. Riddibough G. Developmental biology. Homing in on the homeobox. Nature, 1992, 357(6380): 643-644.
31. Andersen B, Resenfeld MG. POU domain factors in the neuroendocrine system: lessons from developmental biology provide insights into human disease. Endocr Rev, 2001, 22(1):2-35.
32. Hobert O, Westphal H. Functions of LIM-homecbox genes.Trends Genet, 2000, 16(2):75-83.
33. Le Moine C, Young WS. RHS2, A POU domain-containing gene,and its expression in developing and adult rat. Proc Natl Acad Sci USA, 1992, 89(8):3285-3289.
34. Munoz JR, Stoutenger BR, Robinson AP, et al. Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice. Proc Natl Acad Sci USA,2005,102(50):18171-18176.
35. Bovetti S, Bovolin P, Perroteau I , et al. Subventricular zone-derived neuroblast migration to the olfactory bulb is modulated by matrix remodelling. Neuroscience,2007,25(7):2021-2033.
36. McDonald HY,Wojtowiez JM. Dynamics of neurogenesis in the dentate gyrus of adult rats.Neurosci Lett,2005,385(1):70-75.
37. Sugaya K. Neuroreplacement therapy and stem cell biology under disease conditions. Cell Mol Life Sci,2003,60(9):1891-1902.
38.徐慧君。神经生物学。苏州大学出版社,2004:143-158.
39.龙大宏,杨丹迪,李佳楣,等。穹窿海马伞损伤对大鼠学习记忆海马GFAP阳性神经胶质细胞的影响。神经解剖学杂志, 2002, 18 (1) : 63-66.
40. Wu H, Friedman WJ, Dreyfus CF,et a1. Differential regulation of neurotrophin expression in basal forebrain astrocytes by neuronal signals.Neurosci Res,2004,76(1):76-85.
41. Murer MG, Yan Q, Raisman-Vozari R, et a1. Brain-derived neurotrophic factor in the control human brain,and in Alzhelmer’s disease and Parkinson’s disease. Progress in Neurobiology, 2001, 63(1):71-124.
42. Cattaneo E, Mckey R. Proliferation and differentiation of neuronal stem cells regulated by nerve growth factor. Nature, 1990, 347:762- 765.
43. Alderson RF, Alterman AL, Barde YA, et al. Brain-derived neurotrophic factor increases survival and differentiated functions ofrat septal cholinergic neurons in culture. Neuron, 1990, 5(3):297-306.
44.金国华,陈蓉,田美玲,等。海马中56 kD蛋白诱导人神经干细胞向神经元分化的作用。神经解剖学杂志, 2006, 22(4): 389-393.
45. Toncher AB, Yamashima T. Differential neurogenic potential of progenitor cells in dentate gyrus and CA1 sector of the postischemic adult monkey hippocampus. Exp neurol, 2006, 198(1):101-113.
46. Lichtenwalner KJ, Parent JM. Adult neurogenesis and the ischemic forebrain. J Cereb Blood Flow Metab, 2006, 26(1):1-20.
47. Calza L, Giuliani A, Fernandez M, et al. Neural stem cells and cholinergic neurons: Regulation byimmunolesion and treatment with mitogens, retinoic acid, and nerve growth factor. Proc Natl Acad Sci USA, 2003, 100(12):7325-7330.
1. Kaplan DR and Miller FD. Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol, 2000, 10(3): 381-391.
2. Blusztajn JK, Berse B. The cholinergic neuronal phenotype in Alzheimer’S disease. Metabolic Brain Disease, 2000, 15(1):45-64.
3.朱长庚。神经解剖学。北京:人民卫生出版社,2002, 266-268.
4. Rao ZR,Yamano M,Wanaka A,et al. Distribution of cholinergic neurons and fibers in the hypothalamus of the rat using choline acetyltransferase as a marker. Neuroscience, 1987, 20(3): 923-934.
5. Mesulam MM,Avoli M,Reader TA, et al. Central Cholinergic Pathways:Neuroanatomy and some behavioral implications. Neurotransmitters and Cortical Function, 1988, 237-260.
6. Oh JD ,Woolf NJ ,Roghania A, et al. Cholinergic neurons in the rat central nervous system demonstrated by in situ hybridization of choline acetyltransferase mRNA. Neuroscience, 1992, 47(4):807-822.
7. Kasashima S, Muroishi Y, Futakuchi H, et al. In situ mRNA hybridization study of the distribution of choline acetyltransferase in the human brain.Brain Res, 1998, 806(1):8-15.
8.许绍芬。神经生物学。上海:上海医科大学出版社,1999, 142-144.
9. Armstrong DM, Saper CB, Levy AI, et al. Distribution of Cholinergic Neurons in the rat Brain:Demonstrated by the Immunocytomical Localization of Choline Acetyltransferase. J Comp Neurol, 1983, 216(1):53-68.
10. Muir JL. Acetylcholine , aging , and Alzheimer’s disease.Pharmacol Biochem Behav, 1997, 56:687-696.
11. Houser CR, Crawford GD, Salvaterra PM, et al. Immunocytochemical Localization of Choline Acetyltransferase in Rat Cerebral Cortex:A Study of Cholinergic Neurons and Synapses.J Comp Neurol, 1985,234(1):17-34.
12. Cowan WM,Viktor Hamburger, Rita Levi-Montalcin.The path to the discovery of nerve growth factor.Annu Rev Neurosci, 2001, 24: 551-600.
13. Barde YA , Edger D , Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO J, 1982, 1(5):549-553.
14. Leibrock J , Lottspeich H , Hohn A,et al .Molecular cloning and expression of brain derived neurotrophic factor. Nature, 1989, 341(6238):149-152.
15. Wang JM, Zeng YS, Liu RY, et al. Recombinant adenovirus vector -mediated functional expression of neurotropin-3 receptor (TrkC) in neural stem cells. Exp Neurol, 2007, 203 (1):123-127.
16. Ducray A, Kipfer S, Huber AW, et al. Creatine and neurotrophin-4/5 promote survival of nitric oxide synthase - expressing interneurons in striatal cultures. Neurosci Lett, 2006, 395 (1):57 - 62.
17. Berkemeier LR,Ozcelik T, Francke U, et al . Human chromosome 19 contains the neurotrophin-5 gene locus and three related genes that may encode novel acidic neurotrophins . J Somat Cell Mol, 1992, 18(3): 233-245.
18. Li X , Lottspeich F , Gotz R. Recombinant fish neurotrophin-6 is a heparin-binding glycoprotein: implications for a role in axonal guidance. J Biochem ,1997, 324(2):461-466.
19. Nilsson AS, Fainzilber M, Falck P, et al. Neurotrophin-7: a novel member of the neurotrophin family from the zebrafish. FEBS Letters, 1998, 424(3): 285-290.
20. Chao MV. Neurotroph receptors: A window into neuronal differentiation. Neuron, 1992, 9(4):583-593.
21. Kaplan DR, Hempstead BL Marti-Zanca D, et al. The trk proto-oncogene product a signal transducing receptor for nervegrowth factor. Science, 1991, 252(5005):554-558.
22. Ringstedt T, Lagercrantz H and Persson H. Expression of members of the trk family in the developing postnatal rat brain. Brain Res Dev Brain Res, 1993, 72(1):119-131.
23. Lamballe F , Klein R , Barbacid M. TrkC , a new member of the trk family of tyrosine protein kinase , is a receptor for neurotrophin-3. Cell, 1991, 66(5):967-979.
24. Rodrigues-Tebar A, Dechant G and Barde YA. Binding of brain-derived neurotrophic factor to the nerve grow th factor receptor. Neuron, 1990, 4:487-492.
25.蔡文琴,李海标。发育神经生物学。北京:科学出版社,1999,325-327.
26. Wu H, Friedman WJ, Dreyfus CF,et a1. Differential regulation of neurotrophin expression in basal forebrain astrocytes by neuronal signals. Neurosci Res, 2004, 76(1):76-85.
27. Murer MG, Yan Q, Raisman-Vozari R, et a1. Brain-derived neurotrophic factor in the control human brain,and in Alzhelmer’s disease and Parkinson’s disease. Progress in Neurobiology, 2001, 63(1):71-124.
28. Cattaneo E, Mckey R. Proliferation and differentiation of neuronal stem cells regulated by nerve growth factor[J ]. Nature, 1990, 347: 762-765.
29. Ibanez CF. Structure-function relationships in the neurotrophin family. J Neurobiol, 1994, 25(11):1349-1361.
30. Salehi A, Delcroix JD, Swaab DF. Alzheimer’s disease and NGF signaling. J Neural Transm. 2004, 111(3):323-345.
31. Albeck D, Mesches MH, Juthbery S, et al. Exogenous NGF restores endogenous NGF distribution in the brain of the cognitively impaired aged rat. Brain Res, 2003, 967(1-2):306-3l0.
32. Crouley C, Spencer SD, Nishimura MC, et al. Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain chlinergic neurons. Cell, 1994, 76 (16):1001- 1011.
33. Macphee I, Barker PA. Extended ceramide exposure activates the TrkA receptor by increasing receptor homodimer formation. J Neurochem, 1999, 72(4):1423-1430.
34. Kaplan DR, Miller FD. Signal transduction by the neutrophin receptors. Curr Opin Cell Biol, 1997, 9(2):213-221.
35. Holtzman DM, Kilbridge JO, L i YW, et al. TrkA expression in the CNS: evidence for the existence of several novel NGF-responsive CNS neurons. J Neurosci, 1995, 15(2):1567-1576.
36. Gibbs RB, Pfaff DW. In situ hybridization detection of TrkA mRNA in brain: distribution co localization w ith p75NGFR and up regulation by nerve grow th factor. J Comp Neurol, 1994, 341(3):324-339.
37.蔡维君,邓小华,罗学港。大鼠Meynert基底核TrkA和ChAT的表达.神经解剖学杂志,2000, 16(3):234-238.
38. German DC, Yazdani U, Speciale SG, etal. Cholinergic neuropathology in a mouse model of Alzheimer’s disease. J Comp Neurol, 2003, 462(4):371-381.
39. Large TH, Bodary SC, Clegg DO, et al. Nerve growth factor gene expression in the developing rat brain. Science, 1986, 234(4774): 352-355.
40.王永忠,张志坚,刘锦波,姜平,查小英。神经生长因子受体TrkA在新生鼠、幼鼠及成鼠脊髓表达差异的研究。神经解剖学杂志,2002, 18(4):361-362.
41. Altar CA, Cai N, Bliven T, et al. Anterograde transport of brain-derived neurotrophic factor and its role in the brain. Nature, 1997, 389(6653):856-860.
42. Mertz K, Koscheck T, Schilling K. Brain derived neurotrophic factor modulates dend ritic morphology of cerebellar basket and stellate cells:Aninviron study. Neur Science, 2000, 97(2):303-310.
43. Knusel B, Winslow JW, Rosenthal A, et al. Promotion of central cholinergic and dopaminergic neuron differentiation by brain- derived neurotrophic factor but not neurotrophin 3. Proc Natl Acad Sci USA , 1991, 88(3):961-965.
44. Lindsay RM, Wiegand SJ, Altar CA, et al. Neurotrophic factors: from molecule to man. Trends Neurosci, 1994, 17(5):182-190.
45. Alderson RF, Alterman AL, Barde YA, et al. Brain-derived neurotrophic factor increases survival and differentiated functions of rat septal cholinergic neurons in culture. Neuron, 1990, 5(1): 297-306.
46. Martinez-Serrano A, Hantzopoulos PA, Bjorklund A. Ex vivo gene transfer of brain-derived neurotrophic factor to the intact rat forebrain: neurotrophic effects on cholinergic neurons. Eur J Neurosci, 1996, 8(4): 727-735.
47.金国华,徐慧君,武义鸣,等。BDNF、NGF对体外培养的胚胆碱能神经元生长发育的影响。神经解剖学杂志,1997, 13(3):230-234.
48.金国华,徐慧君,武义鸣,等。BDNF、NGF对AD模型鼠脑移植区胚胆碱能神经元发育生长的调控。解剖学报,1999, 30(2):107-112.
49.金国华,田美玲,秦建兵,等。BDNF、NGF对体外长期培养的胚基底前脑胆碱能神经元的影响。神经解剖学杂志,2001, 17(4): 337-341.
50. NonnerD, Barrett JN. Changes in the response of cultured septal cholinergic neurons to nerve growth factor exposure and deprivation during the first postnatal month. Dev Brain Res,1994, 79(2):219- 228.
51. Morse JK, Wiegand SJ, Anderson K, et al. Brain-derived neurotrophic factor (BDNF) prevents the degeneration of medial septal cholinergic neurons following fimbria transection. J Neurosci, 1993, 13 (10):4146 -4156.
52. Iskandrian AS. Adenosine myocardial perfusion imaging. J Nucl Med, 1994, 35(4):734-736.
53. Emfors P. Identification of cells in rat brain and peripheral tissues expressing mRNA for members of the nerve growth factor family. Neuron, 1990, 5(4):511-526.
54. Maisonpierre PC, Belluscio L, Squinto S, et al. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science, 1990, 247(4949): 1446-1451.
55. Novikoval LN, Novikov LN, Kellerth JO. Survival effects of BDNF and NT- 3 on axotomized rubrospinal neurons depend on the temporal pattern of neurotrophin administration. Eur J Neurosci, 2000, 12 (2): 776-780.
56. Zhou XF, Rush RA. Localization of neurotrophin-3-like immunoreactivity in the rat central nervous system. Brain Res, 1994, 643(1-2):162-172.
57. Ip NY, Li Y, Yancopoulos GD, et al. Cultured hippocampal neurons show responses to BDNF, NT-3, and NT-4, but not NGF. J Neurosci, 1993, 13(8):3394-3405.
58. Friedman WJ, Ibanez CF, Hallbook F, et al. Differential actions of neurotrophins in the locus coeruleus and basal forebrain. Exp Neurol, 1993, 119(1):72-78.
59. Lamballe F, Klein R, Barbacid M. TrkC, a new member of the trk family of tyrosine protein kinase, is a receptor for neurotrophin-3. Cell, 1991, 66(5):967-979.
60.刘洁,方秀斌,神经营养因子4/ 5的研究进展。解剖科学进展,2001, 7(3):253-256.
61. Thoenen H. Neurotrophins and neuronal plasticity. Science, 1995, 270(5236):593-598.
62. Stitt NY. Similarities and differences in the way neurotrophins interact with the Trk receptors in neuronal and nonneuronal cells. Neuron, 1993, 10:137-149.
63. Hyman C, J uhasz M. Comparision of the effects of BDNF, NT-3, and NT-4 on dopaminergic and GABAergic neurons of the ventral mesencephalon. J Neurosci, 1994, 14(1):335-347.
64. Ardelt AA, Flaris N, Roth KA. Neurotrophin-4 selectively promotes survival of striatal neurons in organotypic slice culture.Brain Res, 1994, 647(2):340-344.
65. Gtz R, Kster R, Winkler C, et al. Neurotrophin-6 is a new member of the nerve growth factor family. Nature, 1994, 372(6503):266-269.
66. Lai Ko, Fu WY, Ip FC, et al. Cloning and expression of a novel neurotrophin, NT - 7, from carp. Mol Cell Neurosci, 1998, 11 (1-2): 64-76.
67. Wu H, Friedman WJ, Dreyfus CF, et a1. Differential regulation of neurotrophin expression in basal forebrain astrocytes by neuronal signals. Neurosci Res, 2004, 76(1):76-85.
68. Murer MG, Yan Q, Raisman-Vozari R, et a1. Brain-derived neurotrophic factor in the control human brain. and in Alzhelmer’s disease and Parkinson’s disease.Prog Neurobiology, 2001, 63(1): 71-124.
69. Connor B, Dragunow M. The role of neuronal growth factors in neurodegenerative disorders of the human brain. Brain Res Rev, 1998, 27(1):1-39.
70.肖世富,赵瑛,夏斌,等。老年神经精神病学。上海:第二军医大学出版社,2004, 382.
71. Klein RL, Muir D, King MA, et al. Long term action of vector-derived nerve growth factor or brain-derived neurotrophic factor on choline acetyltransferase and trk receptor levels in the adultrat basal forebrain. Neuroscience, 1999, 90(3 ):815-821.
72. Forander P, Soderstrom S, Humpel C, et al. Chronic infusion of nerve growth factor into rat striatum increases cholinergic markers and inhibits striatal neuronal discharge rate. Eur J Neurosci, 1996, 8(9): 1822-1832.
73. Verani MS. Dobutamine myocardial perfusion imaging. J Nucl Med, 1994, 35(4):737-739.
74.龙大宏,姚志彬,李沃棠,等。神经生长因子对老年痴呆鼠学习记忆能力的影响。中国临床康复,2004, 8(10):1951-1953.
75.尹元琴,任常山,陈红,等。阿尔茨海默病模型建立及神经生长因子对ChAT的影响。中国老年学杂志,2004, 24(9):829-831.
76. Swaab DF. Reactivation of atrophic neurons in A1zheimer’s disease. Neurol Res, 2003, 25(6):652-660.
77. Lab SP, Neet KE, Mufson EJ. Nerve growth factor: Structure, function and therapeutic amplications for AIzheimeit’s disease. Curr Drug Target CNS Neurol Disord, 2003, 2(5):315-334.
78. Williams LR, Varon S, Peterson GM,et al. Continuous infusion of nerve growth factor prevents basal forebrain neuronal death after fimbria fornix transection. Proc Natl Acad Sci USA, 1986, 83(23): 9231-9235.
79. Verani MS. Dobutamine myocardial perfusion imaging. J Nucl Med, 1994, 35(4):737-739.
80. Eriksdotter JM, Nordberg A, Amberla K, et al. Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer’s disease. Dement Geriatr Cogn Disord, 1998, 9(5):246-257.
81. HE Yunshao, Yao Zhibin, Chen Yici. Effect of nerve growth factor on the lesioned septohippocampal cholinergic system of aged rats. Brain Res, 1991, 552(1):159-163.
82. Tuszynski MH, Roberts J, Senut MC, et al. Gene therapy in the adultprimate brain: intraparenchymal grafts of cells genetically modified to produce nerve growth factor prevent cholinergic neuronal degeneration. Gene Ther, 1996, 3(4):305-314.
83. Calza L, Giuliani A, Fernandez M, et al. Neural stem cells and cholinergic neurons: Regulation byimmunolesion and treatment with mitogens, retinoic acid, and nerve growth factor. Proc Natl Acad Sci USA, 2003, 100(12):7325-7330.
84. Connor B, Yang D, Yan Q, et a1. Brain-derived neurotrophic factor is reduced in Alzhelmer’s disease. Brain Res Mol, 1997, 49(1-2):71-81.
85. Narisawa-saito M, Wakabayashi K, Tsuji S, et a1. Regimral specificity of alterations jn NGF, BDNF and NT-3 levels in Alzheimer disease. Neuroreport, 1996, 7(18):2925-2928.
86. Fischer W, Sirevaag A, Wiegand SJ, et a1. Reversal of spatial memory impairments in aged rats by nerve growth factor and neurotrophins 3 and 4/5 but not by brain-derived neurotrophic factor. Proc Nail Acad Sci USA, 1994, 91(18):8607-8611.
87. Schober A, Wolf N, Huber K, et al. TrkB and neurotrophin-4 are important for development and maintenance of sympathetic pregangtionic neurons innervating the adrenal medulla. J Neurosci, 1998, 18(18): 7272- 7284.
88.Becker E, Soler RM, Yuste VJ, et al. Development of survival responsiveness to brain-derived neurotrophic factor, neurotrophin 3 and neurotrophin 4/ 5, but not to nerve growth factor, in culturedmotoneurons from chick embryo spinal cord. J Neurosci, 1998, 18(19):7903-7911.