Neuroprotection by neuropeptide Y in cell and animal models of Parkinson's disease
Neuroprotection by neuropeptide Y in cell and animal models of Parkinson's disease
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DOI：
10.1016/j.neurobiolaging.2011.06.018
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发表时间：
2012-09-01
影响因子：
4.2
通讯作者：
Gaillard, Afsaneh
中科院分区：
文献类型：
--
作者：
Decressac, Mickael;Pain, Stephanie;Gaillard, Afsaneh
本研究旨在探讨神经肽Y（NPY）对体外培养的多巴胺能细胞和帕金森病（PD）动物模型中多巴胺能细胞存活的潜在神经保护作用。NPY保护人SH-SY 5 Y多巴胺能神经母细胞瘤细胞免受6-羟基多巴胺诱导的毒性。在PD大鼠和小鼠模型中，纹状体注射NPY可保护黑质纹状体多巴胺通路免于变性，如通过定量（1）黑质丘脑部酪氨酸羟化酶（TH）阳性细胞、（2）纹状体酪氨酸羟化酶和多巴胺转运蛋白水平、（3）多巴胺和3，4-二羟基苯乙酸（DOPAC）以及（4）旋转行为所证明。NPY对Y2受体拮抗剂处理的小鼠和Y2受体缺陷的转基因小鼠无神经保护作用，提示NPY的作用是通过Y2受体介导的。NPY刺激Y2受体可激活ERK 1/2和Akt通路，但不改变脑源性神经营养因子（BDNF）和胶质细胞源性神经营养因子（glial cell line-derived neurotrophic factor，GDF）的水平。这些结果为使用NPY的神经保护疗法开辟了新的前景，并表明在PD中的潜在有益作用。(C)2012 Elsevier Inc. All rights reserved.
This study was aimed to investigate the potential neuroprotective effect of neuropeptide Y (NPY) on the survival of dopaminergic cells in both in vitro and in animal models of Parkinson's disease (PD). NPY protected human SH-SY5Y dopaminergic neuroblastoma cells from 6-hydroxydopamine-induced toxicity. In rat and mice models of PD, striatal injection of NPY preserved the nigrostriatal dopamine pathway from degeneration as evidenced by quantification of (1) tyrosine hydroxylase (TH)-positive cells in the substantia nigra pars compacta, levels of (2) striatal tyrosine hydroxylase and dopamine transporter, (3) dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) as well as (4) rotational behavior. NPY had no neuroprotective effects in mice treated with Y 2 receptor antagonist or in transgenic mice deficient for Y 2 receptor suggesting that NPY effects are mediated through this receptor. Stimulation of Y 2 receptor by NPY triggered the activation of both the ERK1/2 and Akt pathways but did not modify levels of brain derived neurotrophic factor (BDNF) or glial cell line-derived neurotrophic factor. These results open new perspectives in neuroprotective therapies using NPY and suggest potential beneficial effects in PD. (C) 2012 Elsevier Inc. All rights reserved.