Characterization of organotypic ventral mesencephalic cultures from embryonic mice and protection against MPP+ toxicity by GDNF
Characterization of organotypic ventral mesencephalic cultures from embryonic mice and protection against MPP+ toxicity by GDNF
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胚胎小鼠器官型腹侧中脑培养物的表征以及 GDNF 对 MPP 毒性的保护
DOI：
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发表时间：
2005
影响因子：
3.4
通讯作者：
Jens Zimmer
中科院分区：
文献类型：
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作者：
B. Jakobsen;J. Gramsbergen;A. Dall;C. Rosenblad;Jens Zimmer
我们根据多巴胺能神经元数量、细胞体大小和多巴胺产生与体外时间的关系，对来自胚胎 12天（E12）小鼠（CBL57/bL6）的器官型腹侧中脑（VM）培养物进行了表征，并测试了1-甲基-4-苯基吡啶鎓（MPP+）和神经胶质源性神经营养因子的作用 （GDNF）来验证这种新颖的文化模型。在体外，多巴胺产生和多巴胺能神经元胞体大小随着时间的推移而急剧增加，而多巴胺神经元数量在第 1周和第 2周之间下降了约30%，第 4周后进一步减少。GDNF治疗（100 ng/mL）增加了多巴胺能神经元胞体大小（高达43%）和DOPAC产生（约三倍），但没有增加 对照培养物中的多巴胺神经元。一周龄的培养物比三周龄的培养物更容易受到 MPP+ 的影响。暴露 2 天和恢复 15 天后多巴胺消耗的 EC50 分别为 0.6 和 7μm。 GDNF 预处理和后处理对于获得针对 MPP+ 毒性的最大保护非常重要。在一周龄的培养物（5μm MPP+，2天）中，GDNF提供了有效的神经保护作用，多巴胺含量达到对照水平，酪氨酸羟化酶（TH）+细胞数量达到对照的80%，但在三周龄的培养物（10μm MPP+，2天）中，GDNF的保护潜力显着降低。 MPP+ 暴露后需要较长的恢复期才能区分可逆或不可逆的毒性和/或营养效应。
We characterized organotypic ventral mesencephalic (VM) cultures derived from embryonic day 12 (E12) mice (CBL57/bL6) in terms of number of dopaminergic neurons, cell soma size and dopamine production in relation to time in vitro and tested the effects of 1‐methyl‐4‐phenylpyridinium (MPP+) and glial derived neurotrophic factor (GDNF) to validate this novel culture model. Dopamine production and dopaminergic neuron soma size increased dramatically with time in vitro, whereas the number of dopamine neurons declined by approximately 30% between week 1 and week 2, which was further reduced after week 4. GDNF treatment (100 ng/mL) increased dopaminergic neuron soma size (up to 43%) and DOPAC production (approximately three‐fold), but not the number of dopamine neurons in control cultures. One‐week‐old cultures were more vulnerable to MPP+, than three‐week‐old cultures. The EC50 for dopamine depletion after 2 days exposure and 15 days of recovery were 0.6 and 7 µm, respectively. Both pre‐treatment and post‐treatment with GDNF are important to obtain maximal protection against MPP+ toxicity. In one‐week‐old cultures (5 µm MPP+, 2 days) GDNF provided potent neuroprotection with dopamine contents reaching control levels and number of tyrosine hydroxylase (TH)+ cells up to 80% of control, but in three‐week‐old cultures (10 µm MPP+, 2 days) the protective potential of GDNF was markedly reduced. Long recovery periods after MPP+ exposure are required to distinguish between reversible or irreversible toxic and/or trophic effects.
影响因子：
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作者：
Irwin,I;DeLanney,LE;Langston,JW
通讯作者：
Langston,JW