A study on the mechanism of MPP^+ neurotoxicity in culture of fatal rat doperminergic neurons

致死性大鼠多巴胺能神经元培养中MPP^神经毒性机制的研究

• 批准号: 06670677
• 负责人: TAKAHASHI Mitsuo
• 金额: $ 1.28万
• 依托单位: Kinki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06670677/
• 关键词: Parkinsons Disease; MPP neurotoxicity; fatal rat brain; Dopaminergic neuron; NGF; BDNF; Free radical; Interleukin; ドバミナージックニウロン; ドーパミナージックニューロン; パーキンソン病; coculture; MPP^+; 酸; 標的由来神経栄養因子; 中脳黒質

To study on the mechanism of MPP^+ neurotoxicity against doperminergic neurons (DN), the vulneravility of cultured cells from the ventral mesencephalon of embryonic 17 days rats under MPP^+ was evaluated with free radical, nerve growth factor, or interleukin.We have shown that DN may be exclusively sensitive to elevated acidity elicited after the addition of glial mitogenic factors such as epidermal growth factor and basic fibroblast growth factor or after the direct treatment with hydrochloric acid.The acid sensitivity was specific to DN and was inhibited by addition of brain-derived neurotrophic factor (BDNF).Such antioxidants as VE,VC,CoQ_<10> and catalase, but neither allopurinol nor superoxide dismutase, alleviated the MPP^+ induced death of DN,while glutamate receptor did not alter MPP^+ neurotoxicity.Concerning interleukin (IL), IL-1beta was showed to act as a neurotrophic factor on DN,and IL-6 was revealed to be able of protecting DN from the neurotoxicity of MPP^+ without glial proliferation.

为探讨MPP^+对多巴胺能神经元（DN）的神经毒性作用机制，采用自由基、神经生长因子和白细胞介素评价MPP^+对胚胎17天大鼠腹侧中脑培养细胞的易损性。我们已经表明，DN可能只对添加胶质细胞有丝分裂因子（如表皮生长因子和碱性成纤维细胞生长因子）或直接用盐酸处理后引起的酸度升高敏感。DN特异性的酸敏感性可通过添加脑源性神经营养因子（BDNF）来抑制。除别嘌呤醇和超氧化物歧化酶外，VE、VC、CoQ_<10>和过氧化氢酶等抗氧化剂均不能减轻MPP^+诱导的DN死亡，而谷氨酸受体对MPP^+的神经毒性没有影响。关于白细胞介素（IL）， IL-1 β被证明是DN的一种神经营养因子，IL-6被证明能够保护DN免受MPP^+的神经毒性而不产生胶质细胞增殖。

项目成果

Yukio Akaneya,Mitsuo Takahashi,Hiroshi Hatanaka: "Involvment of free radicals in MPP^+neurotoxicity against rat dopaminergic neurons in culture" Neuroscience Letters. 193. 53-56 (1995)

Yukio Akaneya、Mitsuo Takahashi、Hiroshi Hatanaka：“自由基参与 MPP^ 对培养物中大鼠多巴胺能神经元的神经毒性”《神经科学快报》。

Yukio Akaneya,Mitsuo Takahashi,Hiroshi Hatanaka: "Interlsukin-1 β Enhances Survival and Interleukin-6 Protects against MPP^+ Neurotoxicity in Cultures of Fetal Rat Dopaminergic Neurons" Experimental Neurology. 136. 44-52 (1995)

Yukio Akaneya、Mitsuo Takahashi、Hiroshi Hatanaka：“Interlsukin-1 β 增强胎儿大鼠多巴胺能神经元培养物中的存活率和 Interleukin-6 防止 MPP^+ 神经毒性”实验神经学 136. 44-52 (1995)。

Yukio Akaneya,Mitsuo Takahashi,Hiroshi Hatanaka: "Survival of and 1-methyl 4-phenylpyridinium (MPP^+) neurotoxicity against dopaminergic neurons in coculture of rat mesencephalon with their target or nontarget regions" Neuroscience Research. 23. 55-63 (19

Yukio Akaneya、Mitsuo Takahashi、Hiroshi Hatanaka：“大鼠中脑与其目标或非目标区域共培养中多巴胺能神经元的存活和 1-甲基 4-苯基吡啶 (MPP^) 神经毒性”神经科学研究。

Mitsuo Takahashi,Ryoichi Yuasa,Terukuni Imai,et al: "Selegline(L-Deprenyl)and L-Dopa Treatment of Parkinson's Disease:A Double Blind Trial" Internal Medicine. 33. 517-524 (1995)

Mitsuo Takahashi、Ryoichi Yuasa、Terukuni Imai 等：“Selegline（L-Deprenyl）和 L-Dopa 治疗帕金森病：双盲试验”内科。

Yukio Akaneya, Mitsuo Takahashi, Hiroshi Hatanaka: "Involvment of free radicals in MPP^+ neurotoxicity against rat dopaminergic neurons in culture." Neuroscience Letters. 193. 53-56 (1995)

Yukio Akaneya、Mitsuo Takahashi、Hiroshi Hatanaka：“自由基参与 MPP^ 对培养物中大鼠多巴胺能神经元的神经毒性。”