Transforming growth factor beta2 haploinsufficient mice develop age-related nigrostriatal dopamine deficits
Transforming growth factor beta2 haploinsufficient mice develop age-related nigrostriatal dopamine deficits
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DOI：
10.1016/j.nbd.2005.09.001
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发表时间：
2006-03-01
影响因子：
6.1
通讯作者：
McLennan, IS
中科院分区：
文献类型：
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作者：
Andrews, ZB;Zhao, H;McLennan, IS
转化生长因子-β (TGF-β) 调节多巴胺能神经元的诱导，并在帕金森病患者的脑脊液中升高。我们在此报告，TGF-β 2 单倍体不足 (TGF-β 2(+/-)) 的小鼠在其黑质致密部的多巴胺能神经元中存在亚临床缺陷。 6 周龄时，TGF-β 2(+/-) 小鼠的多巴胺能神经元比野生型同窝小鼠少 12%。在接下来的 5 个月内，虽然纹状体多巴胺下降至正常值的 70%，但没有发生额外的神经元损失。 TGF-β2(+/-) 小鼠的 3,4-二羟基苯乙酸水平正常，表明补偿机制维持了纹状体的多巴胺刺激。尽管单胺氧化酶-B 水平降低，但 TGF-β 2(+/-) 小鼠对神经毒素 1-甲基-4-苯基-1,2,3,6-四氢吡啶具有正常敏感性。这些结果表明，TGF-β2 水平天然较低的人的黑质纹状体通路的功能储备可能较少，从而导致他们患帕金森病的风险增加。 (C) 2005 Elsevier Inc. 保留所有权利。
The transforming growth factor-betas (TGF-beta s) regulate the induction of dopaminergic neurons and are elevated in the CSF of Parkinson's patients. We report here that mice with TGF-beta 2 haploinsufficiency (TGF-beta 2(+/-)) have subclinical defects in the dopaminergic neurons of their substantia nigra pars compacta. At 6 weeks of age, the TGF-beta 2(+/-) mice had 12% fewer dopaminergic neurons than wild-type littermates. No additional loss of neurons occurred during the next 5 months, although striatal dopamine declined to 70% of normal. The level of 3,4-dihydroxphenylacetic acid was normal in the TGF-beta 2(+/-) mice, indicating that a compensatory mechanism maintains dopamine stimulation of their striatum. The TGF-beta 2(+/-) mice had normal sensitivity to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tretrahydropyridine, despite having reduced levels of monoamine oxidase-B. These results raise the possibility that people with naturally low levels of TGF-beta 2 may have less functional reserve in their nigrostriatal pathway, causing them to be at increased risk of developing Parkinson disease. (C) 2005 Elsevier Inc. All rights reserved.