目的 考察骨髓间充质干细胞(MSC)移植对Tourette综合征(TS)大鼠纹状体内脑源性神经营养因子(BDNF)表达的影响,探讨MSC移植治疗TS的作用机制。方法 采用立体定向技术向大鼠纹状体内微量灌注抗基底神经节抗体(ABGA),制备自身免疫TS动物模型;采用密度梯度离心法在体外分离、培养和扩增大鼠MSC,经流式细胞仪鉴定后将MSC标记并移植到TS大鼠纹状体内。通过ELISA及RT-PCR技术检测大鼠脑内BDNF水平。结果 将MSC移植到TS大鼠纹状体内,自移植后7 d开始观察到TS大鼠的刻板行为减少。TS大鼠纹状体内BDNF水平升高(P<0.05);MSC移植后TS大鼠纹状体内BDNF含量下降。结论 MSC移植能减少TS大鼠的刻板行为、降低TS大鼠体内的BDNF含量。
Abstract
Objective To investigate bone marrow mesenchymal stem cells (MSC) transplantation on brain-derived neurotrophic factor (BDNF) expression in the striatum of Tourette syndrome (TS) rat,and to explore the possible mechanism of MSC transplantation in the treatment of TS. Methods Seventy-two Wistar rats were randomly allocated to the control group and the two experimental groups,namely,TS rats+vehicle and TS rats+MSC.MSCs were co-cultured with 5-bromodeoxyuridine (BrdU) for 24 h for labeling prior to grafting.An autoimmune TS animal model was adopted in the present study.Rat MSCs were cultured and expanded using density gradient centrifugation in vitro,identified by flow cytometry and transplanted into the striatums of TS animal.BDNF level was detected by ELISA and RT-PCR techniques. Results Stereotypic behaviors reduced in TS rats 7 days after MSC transplantation into rat striatum.BDNF level in striatum of TS rat increased (P<0.05).After MSC transplantation,the BDNF level decreased in the striatum of TS rat. Conclusions Intrastriatal transplantation of MSCs can provide relief from the stereotypic behavior of TS.BDNF level reduces in TS rats after MSC transplantation.
关键词
骨髓间充质干细胞 /
移植 /
Tourette综合征 /
脑源性神经营养因子
Key words
bone marrow mesenchymal stem cells /
transplantation /
Tourette syndrome /
brain-derived neurotrophic factor
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Tamara P.Tourette syndrome and other tic disorders of childhood[J].Handb Clin Neurol,2013,112:853-856.
[2] Liu X,Wang Y,Li D,et al.Transplantation of rat neural stem cells reduces stereotypic behaviors in rats after intrastriatal microinfusion of Tourette syndrome sera[J].Behav Brain Res,2008,186(1):84-90.
[3] Liu XM,Wang YW,Yi MJ.Effects of human mesenchymal stem cell transplantation in the bilateral corpus striatum in a rat model of Tourette's syndrome[J].Neural Regen Res.2010,5(17):1285-1290.
[4] Van Velthoven CT,Braccioli L,Willemen HL,et al.Therapeutic potential of genetically modified mesenchymal stem cells after neonatal hypoxic-ischemic brain damage[J].Mol Ther,2014,22(3):645-654.
[5] Taylor JL,Rajbhandari AK,Berridge KC,et al.Dopamine receptor modulation of repetitive grooming actions in the rat:potential relevance for Tourette syndrome[J].Brain Res,2010,1322:92-101.
[6] Malaty IA,Akbar U.Updates in medical and surgical therapies for Tourette syndrome[J].Curr Neurol Neurosci Rep,2014,14(7):458.
[7] Kordi-Tamandani DM,Sahranavard R,Torkamanzehi A.DNA methylation and expression profiles of the brain-derived neurotrophic factor (BDNF) and dopamine transporter (DAT1) genes in patients with schizophrenia[J].Mol Biol Rep,2012,39(12):10889-10893.
[8] Ferrini F,De Koninck Y.Microglia control neuronal network excitability via BDNF signaling[J].Neural Plast,2013,2013:429815
[9] Phinney DG,Isakova IA.Mesenchymal stem cells as cellular vectors for pediatric neurological disorders[J].Brain Res,2014,1573:92-107.
[10] Zhang F,Wang YY,Liu H,et al.Resveratrol produces neurotrophic effects on cultured dopaminergic neurons through prompting astroglial BDNF and GDNF release[J].Evid Based Complement Alternat Med,2012,2012:937605.doi:10.1155/2012/937605.
[11] Paulsen JS.Cognitive impairment in Huntington disease:diagnosis and treatment[J].Curr Neurol Neurosci Rep,2011,11(5):474-483.
[12] Niitsu T,Shirayama Y,Matsuzawa D,et al.Associations of serum brain-derived neurotrophic factor with cognitive impairments and negative symptoms in schizophrenia[J].Prog Neuropsychopharmacol Biol Psychiatry,2011,35(8):1836-1840.
[13] Mang CS,Campbell KL,Ross CJ,et al.Promoting neuroplasticity for motor rehabillitation after stroke:considering the effects of aerobic exercise and genetic variation on brain-derived neurotrophic factor[J].Phys Ther,2013,93(12):1707-1716.
[14] Shimada H,Makizako H,Doi T,et al.A large,cross-sectional observational study of serum BDNF,cognitive function,and mild cognitive impairment in the elderly[J].Front Aging Neurosci,2014,6:69.
[15] Li Y,Yui D,Luikart BW,et al.Conditional ablation of brain-derived neurotrophic factor-TrkB signaling impairs striatal neuron development[J].Proc Natl Acad Sci USA,2012,109(38):15491-15496.
[16] Martino D,Chiarotti F,Buttiglione M,et al.The relationship between group A streptococcal infections and Tourette syndrome:a study on a large service-based cohort[J].Dev Med Child Neurol,2011,53(10):951-957.
[17] Yeh TK,Hu CY,Yeh TC,et al.Association of polymorphisms in BDNF,MTHFR,and genes involved in the dopaminergic pathway with memory in a healthy Chinese population[J].Brain Cogn,2012,80(2):282-289.
基金
国家自然科学基金(81101017);山东省优秀中青年科学家科研奖励基金(BS2010F030);烟台市科学技术发展计划项目(2010148-24)
PDF(601 KB)
