Neuropathological and therapeutic studies on adult motoneuron degeneration using rat peripheral nerve avulsion models

使用大鼠周围神经撕脱模型对成人运动神经元变性进行神经病理学和治疗研究

• 批准号: 14570627
• 负责人: WATABE Kazuhiko
• 金额: $ 2.18万
• 依托单位: Tokyo Metropolitan Organization for Medical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570627/
• 关键词: Adenovirus vector; Avulsion; Facial nerve; Motoneuron; Neurotrophic factor; ALS; Schwann cell; SOD1

We have utilized adult rat peripheral nerve avulsion models to evaluate the effects of neuroprotective molecules on motoneuron degeneration. The right facial nerves of adult Fischer 344 male rats were avulsed and adenoviral vectors encoding glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), transforming growth factor-β2 (TGFβ2), and growth inhibitory factor (GIF) were injected into the facial canal. The treatment with the vectors significantly prevented the loss of lesioned facial motoneurons, improved choline acetyltransferase (ChAT) immunoreactivity and suppressed the induction of nitric oxide synthase activity in these neurons. In separate experiments, animals were orally administered solution of a neuroprotective compound T-588 after avulsion. Both free oral administration and oral tube administration of T-588 improved the survival of injured motoneurons and ameliorated their ChAT immunoreactivity. These results indicate that the gene transfer of GDNF, BDNF, TGFβ2, and GIF and oral administration of T-588 may prevent the degeneration of motoneurons in adult humans with motoneuron injury and motor neuron diseases.

我们利用成年大鼠周围神经撕脱模型来评估神经保护分子对运动神经元变性的影响。将成年Fischer 344雄性大鼠右侧面神经撕脱，并将编码胶质细胞系源性神经营养因子（GDNF）、脑源性神经营养因子（BDNF）、转化生长因子-β2（TGFβ2）和生长抑制因子（GIF）的腺病毒载体注射到面神经管内。与载体的治疗显着防止损失的损伤面运动神经元，改善胆碱乙酰转移酶（ChAT）的免疫反应性和抑制诱导的一氧化氮合酶活性在这些神经元。在单独的实验中，动物在撕脱后口服神经保护化合物T-588的溶液。T-588的自由口服给药和口服管给药均改善了受损运动神经元的存活，并改善了其ChAT免疫反应性。这些结果表明，GDNF、BDNF、TGFβ2和GIF的基因转移和口服T-588可以预防成年人运动神经元损伤和运动神经元疾病的运动神经元变性。

项目成果

Establishment and characterization of spontaneously immortalized Schwann cells from murine model of globoid cell leukodystrophy (twitcher)

• DOI: 10.1002/jnr.10247
• 发表时间: 2002-06-01
• 期刊: JOURNAL OF NEUROSCIENCE RESEARCH
• 影响因子: 4.2
• 作者: Shen, JS;Watabe, K;Eto, Y
• 通讯作者: Eto, Y

Sendai virus vector-mediated gene transfer of glial cell line-derived neurotrophic factor prevents delayed neuronal death after transient global ischemia in gerbils.

仙台病毒载体介导的神经胶质细胞系源性神经营养因子的基因转移可防止沙鼠短暂性整体缺血后延迟性神经元死亡。

• 发表时间: 2003
• 期刊: Exp Anim 52
• 作者: Shirakura M;Fukumura M;Inoue M;Fujikawa S;Maeda M;Watabe K;Kyuwa S;Yoshikawa Y;Hasegawa M
• 通讯作者: Hasegawa M

Oral administration of a neuroprotective compound T-588 prevents motoneuron degeneration after facial nerve avulsion in adult rats

口服神经保护化合物 T-588 可预防成年大鼠面神经撕脱后的运动神经元变性

• 发表时间: 2003
• 期刊: Amyotroph Lateral Scler Other Motor Neuron Disord 4
• 作者: Ikeda;K.;Sakamoto;T.;Kawazoe;Y.;Marubuchi;S.;Nakagawa;M.;Ono;S.;Terashima;N.;Kinoshita;M.;Iwasaki;Y.;Watabe;K.
• 通讯作者: K.

Tissue culture methods to study neurological disorders : Establishment of immortalized Schwann cells from murine disease models.

研究神经系统疾病的组织培养方法：从小鼠疾病模型中建立永生化雪旺细胞。

• 发表时间: 2003
• 期刊: Neuropathology 23
• 作者: Watabe K;Sakamoto T;Kawazoe Y;Michikawa M;Miyamoto K;Yamamura T;Saya H;Araki N.
• 通讯作者: Araki N.

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