A New Transgenic Mouse Model for Studying the Neurotoxicity of Spermine Oxidase Dosage in the Response to Excitotoxic Injury.
A New Transgenic Mouse Model for Studying the Neurotoxicity of Spermine Oxidase Dosage in the Response to Excitotoxic Injury.
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DOI：
10.1371/journal.pone.0064810
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Mariottini P
中科院分区：
文献类型：
--
作者：
Cervelli M;Bellavia G;D'Amelio M;Cavallucci V;Moreno S;Berger J;Nardacci R;Marcoli M;Maura G;Piacentini M;Amendola R;Cecconi F;Mariottini P
精胺氧化酶是一种含有FAD的酶，参与多胺催化，选择性氧化精胺产生H2 O2、亚精胺和3-氨基丙醛。精胺氧化酶在小鼠脑中高度表达，并在调节精胺水平方面起关键作用，精胺参与蛋白质合成、细胞分裂和细胞生长。精胺通常由神经元在突触部位释放，通过与不同类型的离子通道和离子型谷氨酸受体特异性相互作用，发挥神经调节功能。为了深入了解精胺氧化酶和精胺的神经生物学作用，我们解除了精胺氧化酶基因表达的调节，产生并表征了转基因小鼠模型JoSMOrec，在新皮质中有条件地过表达该酶。我们研究了精胺氧化酶过表达的影响，在小鼠新皮层的转录积累，免疫组织化学分析，酶测定和多胺含量在年轻和老年动物。转基因JoSMOrec小鼠在新皮质中显示出相对于野生型对照更高的H2 O2产生，表明由于SMO过表达导致的氧化应激增加。此外，通过分析行为表型，神经细胞群的免疫分布和新皮层神经元的超微结构特征，转基因小鼠兴奋性毒性脑损伤，诱导红藻氨酸注射液的反应进行了评价。精胺氧化酶过度表达和由此改变的多胺水平在新皮质影响细胞结构在成人和老龄化的大脑，以及神经毒性损伤后。结果表明，转基因JoSMOrec小鼠系比野生型小鼠对KA更敏感，表明精胺氧化酶在兴奋性毒性中起重要作用。这些结果为精胺氧化酶和精胺在哺乳动物脑中的复杂和关键功能提供了新的证据。
Spermine oxidase is a FAD-containing enzyme involved in polyamines catabolism, selectively oxidizing spermine to produce H2O2, spermidine, and 3-aminopropanal. Spermine oxidase is highly expressed in the mouse brain and plays a key role in regulating the levels of spermine, which is involved in protein synthesis, cell division and cell growth. Spermine is normally released by neurons at synaptic sites where it exerts a neuromodulatory function, by specifically interacting with different types of ion channels, and with ionotropic glutamate receptors. In order to get an insight into the neurobiological roles of spermine oxidase and spermine, we have deregulated spermine oxidase gene expression producing and characterizing the transgenic mouse model JoSMOrec, conditionally overexpressing the enzyme in the neocortex. We have investigated the effects of spermine oxidase overexpression in the mouse neocortex by transcript accumulation, immunohistochemical analysis, enzymatic assays and polyamine content in young and aged animals. Transgenic JoSMOrec mice showed in the neocortex a higher H2O2 production in respect to Wild-Type controls, indicating an increase of oxidative stress due to SMO overexpression. Moreover, the response of transgenic mice to excitotoxic brain injury, induced by kainic acid injection, was evaluated by analysing the behavioural phenotype, the immunodistribution of neural cell populations, and the ultrastructural features of neocortical neurons. Spermine oxidase overexpression and the consequently altered polyamine levels in the neocortex affects the cytoarchitecture in the adult and aging brain, as well as after neurotoxic insult. It resulted that the transgenic JoSMOrec mouse line is more sensitive to KA than Wild-Type mice, indicating an important role of spermine oxidase during excitotoxicity. These results provide novel evidences of the complex and critical functions carried out by spermine oxidase and spermine in the mammalian brain.
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影响因子：
3.4
作者：
HALONEN, T;SIVENIUS, J;RIEKKINEN, PJ
通讯作者：
RIEKKINEN, PJ
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Kaasinen, SK;Gröhn, OHJ;Jänne, J
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Turecki, Gustavo
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作者：
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