Susceptibility to a parkinsonian toxin varies during primate development.
Susceptibility to a parkinsonian toxin varies during primate development.
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DOI：
10.1016/j.expneurol.2012.02.005
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发表时间：
2012-05
影响因子：
5.3
通讯作者：
Elsworth, J. D.
中科院分区：
文献类型：
--
作者：
Morrow, B. A.;Roth, R. N.;Redmond, D. E., Jr.;Diano, S.;Elsworth, J. D.
当黑质纹状体多巴胺神经元功能丧失超过基底神经节代偿机制的阈值时，帕金森病的症状通常会在晚年出现。尽管黑质纹状体多巴胺神经元在衰老过程中会丢失，但在帕金森病中，其他有害因素一定发挥了作用，导致这些神经元的损失超过正常水平。人们假设早期发育是一个潜在的脆弱时期，环境或遗传异常可能会损害中枢多巴胺神经元。本研究使用一种特定的帕金森神经毒素，1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP），来探讨灵长类动物发育不同阶段黑质纹状体多巴胺神经元的相对脆弱性。对多巴胺、高香草酸、1-甲基吡啶浓度和酪氨酸羟化酶免疫反应性神经元的测量表明，妊娠中期的多巴胺神经元相对容易受到 MPTP 的影响，而在发育后期或幼年灵长类动物中，这些神经元对神经毒素具有抵抗力。这些研究强调了胎儿在妊娠中期接触引起氧化应激的环境因素可能面临更大的风险。此外，数据表明，解偶联 Protein-2 可能是延缓帕金森病和衰老过程中黑质纹状体多巴胺神经元逐渐丧失的目标。
Symptoms of Parkinson’s disease typically emerge later in life when loss of nigrostriatal dopamine neuron function exceeds the threshold of compensatory mechanisms in the basal ganglia. Although nigrostriatal dopamine neurons are lost during aging, in Parkinson’s disease other detrimental factors must play a role to produce greater than normal loss of these neurons. Early development has been hypothesized to be a potentially vulnerable period when environmental or genetic abnormalities may compromise central dopamine neurons. This study uses a specific parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), to probe the relative vulnerability of nigrostriatal dopamine neurons at different stages of primate development. Measures of dopamine, homovanillic acid, 1-methyl-pyridinium concentrations and tyrosine hydroxylase immunoreactive neurons indicated that at mid-gestation dopamine neurons are relatively vulnerable to MPTP, whereas later in development or in the young primate these neurons are resistant to the neurotoxin. These studies highlight a potentially greater risk to the fetus of exposure during mid-gestation to environmental agents that cause oxidative stress. In addition, the data suggest that uncoupling protein-2 may be a target for retarding the progressive loss of nigrostriatal dopamine neurons that occurs in Parkinson’s disease and aging.
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影响因子：
12.7
作者：
FURUNE, S;MIURA, K;NAGATSU, I
通讯作者：
NAGATSU, I
影响因子：
6.7
作者：
Brown AS
通讯作者：
Brown AS
影响因子：
2.5
作者：
Chu, YP;Kompoliti, K;Kordower, JH
通讯作者：
Kordower, JH
影响因子：
64.8
作者：
Echtay, KS;Winkler, E;Klingenberg, M
通讯作者：
Klingenberg, M
DOI：
10.1073/pnas.80.14.4546
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
BURNS, RS;CHIUEH, CC;KOPIN, IJ
通讯作者：
KOPIN, IJ