Omega-3 deficiency and neurodegeneration in the substantia nigra: Involvement of increased nitric oxide production and reduced BDNF expression
Omega-3 deficiency and neurodegeneration in the substantia nigra: Involvement of increased nitric oxide production and reduced BDNF expression
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DOI：
10.1016/j.bbagen.2013.12.023
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发表时间：
2014-06-01
影响因子：
3
通讯作者：
da Silveira Andrade-da-Costa, Belmira Lara
中科院分区：
文献类型：
--
作者：
Cardoso, Henriqueta Dias;dos Santos Junior, Eraldo Fonseca;da Silveira Andrade-da-Costa, Belmira Lara
背景资料：我们以前的研究表明，必需脂肪酸（EFA）的饮食限制超过两代诱导中脑多巴胺能细胞的损失和氧化应激的黑质（SN），但不是在纹状体的年轻大鼠。在本研究中，我们假设，欧米茄-3缺乏症，直到成年将减少纹状体的弹性，增加一氧化氮（NO）水平和BDNF表达的神经元的数量，这两个潜在的机制参与SN neurodegeneration.Methods：第二代大鼠从妊娠控制或EFA限制饮食，直到年轻或成年。测定黑质和纹状体的脂质过氧化、NO含量、总超氧化物歧化酶（t-SOD）和过氧化氢酶活性。酪氨酸羟化酶（TH）和BDNF表达神经元的数量进行了分析，在SN。结果：增加NO水平观察到在纹状体的年轻和成年EFA缺乏的动物，但不是在SN，尽管类似的omega-3耗尽（类似65%）在这些地区。增加脂质过氧化和过氧化氢酶活性下降，发现在这两个地区，而较低的tSOD活性只观察到在纹状体。较少的TH-（类似于40%）和BDNF阳性细胞（类似于20%）被检测到在SN相比，control.Conclusion：目前的研究结果表明，在大鼠的黑质纹状体系统的NO生产的omega-3缺乏的差异效应。延长欧米茄-3耗尽，直到成年受损纹状体的抗氧化剂资源和BDNF分布在SN，恶化dopaminergic细胞degeneration.General意义：欧米茄-3缺乏可以降低黑质纹状体系统的能力，以维持在氧化条件下的稳态，这可能会增加帕金森氏病的风险。0（C）2013 Elsevier B. V.保留所有权利。
Background: Our previous study demonstrated that essential fatty acid (EFA) dietary restriction over two generations induced midbrain dopaminergic cell loss and oxidative stress in the substantia nigra (SN) but not in the striatum of young rats. In the present study we hypothesized that omega-3 deficiency until adulthood would reduce striatum's resilience, increase nitric oxide (NO) levels and the number of BDNF-expressing neurons, both potential mechanisms involved in SN neurodegeneration.Methods: Second generation rats were raised from gestation on control or EFA-restricted diets until young or adulthood. Lipoperoxidation, NO content, total superoxide dismutase (t-SOD) and catalase enzymatic activities were assessed in the SN and striatum. The number of tyrosine hydroxylase (TH)- and BDNF-expressing neurons was analyzed in the SN.Results: Increased NO levels were observed in the striatum of both young and adult EFA-deficient animals but not in the SN, despite a similar omega-3 depletion (similar to 65%) in these regions. Increased lipoperoxidation and decreased catalase activity were found in both regions, while lower tSOD activity was observed only in the striatum. Fewer TH- (similar to 40%) and BDNF-positive cells (similar to 20%) were detected at the SN compared to the control.Conclusion: The present findings demonstrate a differential effect of omega-3 deficiency on NO production in the rat's nigrostriatal system. Prolonging omega-3 depletion until adulthood impaired striatum's anti-oxidant resources and BDNF distribution in the SN, worsening dopaminergic cell degeneration.General significance: Omega-3 deficiency can reduce the nigrostriatal system's ability to maintain homeostasis under oxidative conditions, which may enhance the risk of Parkinson's disease. 0 (C) 2013 Elsevier B.V. All rights reserved.