Reactive Astrocytosis in a Mouse Model of Chronic Polyamine Catabolism Activation.
Reactive Astrocytosis in a Mouse Model of Chronic Polyamine Catabolism Activation.
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DOI：
10.3390/biom11091274
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发表时间：
2021-08-25
期刊：
影响因子：
5.5
通讯作者：
Cervelli M
中科院分区：
文献类型：
--
作者：
Cervetto C;Averna M;Vergani L;Pedrazzi M;Amato S;Pelassa S;Giuliani S;Baldini F;Maura G;Mariottini P;Marcoli M;Cervelli M
背景资料：在脑中，多胺主要在神经元中合成，但优先在星形胶质细胞中积累，并且被认为参与神经变性/神经炎性疾病和神经元损伤。在新皮层神经元中过表达精胺氧化酶（SMOX，其特异性氧化精胺）的转基因小鼠（Dach-SMOX小鼠）被证明是对兴奋性毒性损伤的易感性增加的模型。研究方法：为了研究Dach-SMOX小鼠中突触功能的可能改变，通过评估多胺水平、埃兹蛋白和波形蛋白含量、谷氨酸AMPA受体活化、钙内流和过氧化氢酶活性来分析皮质神经末梢（突触体）和星形胶质细胞过程（胶质体）。结果如下：主要发现如下：（i）在对照和Dach-SMOX小鼠的突触体中以及仅在Dach-SMOX小鼠的胶质体中存在功能性钙渗透AMPA受体;（ii）Dach-SMOX小鼠胶质体中精胺含量降低;（iii）Dach-SMOX小鼠突触体和胶质体中过氧化氢酶活性分别下调和上调。结论：神经元中SMOX的慢性激活导致星形胶质细胞过程的重大变化，包括精胺水平降低、通过钙渗透性AMPA受体的钙内流增加以及过氧化氢酶活性的刺激。星形细胞增多症和星形胶质细胞过程的改变，依赖于多胺catalysts的慢性激活，导致突触失调和神经元的痛苦。
Background: In the brain, polyamines are mainly synthesized in neurons, but preferentially accumulated in astrocytes, and are proposed to be involved in neurodegenerative/neuroinflammatory disorders and neuron injury. A transgenic mouse overexpressing spermine oxidase (SMOX, which specifically oxidizes spermine) in the neocortex neurons (Dach-SMOX mouse) was proved to be a model of increased susceptibility to excitotoxic injury. Methods: To investigate possible alterations in synapse functioning in Dach-SMOX mouse, both cerebrocortical nerve terminals (synaptosomes) and astrocytic processes (gliosomes) were analysed by assessing polyamine levels, ezrin and vimentin content, glutamate AMPA receptor activation, calcium influx, and catalase activity. Results: The main findings are as follows: (i) the presence of functional calcium-permeable AMPA receptors in synaptosomes from both control and Dach-SMOX mice, and in gliosomes from Dach-SMOX mice only; (ii) reduced content of spermine in gliosomes from Dach-SMOX mice; and (iii) down-regulation and up-regulation of catalase activity in synaptosomes and gliosomes, respectively, from Dach-SMOX mice. Conclusions: Chronic activation of SMOX in neurons leads to major changes in the astrocyte processes including reduced spermine levels, increased calcium influx through calcium-permeable AMPA receptors, and stimulation of catalase activity. Astrocytosis and the astrocyte process alterations, depending on chronic activation of polyamine catabolism, result in synapse dysregulation and neuronal suffering.
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影响因子：
3.7
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
通讯作者：
Mariottini P
影响因子：
4.8
作者：
Antony, T;Hoyer, W;Subramaniam, V
通讯作者：
Subramaniam, V
DOI：
10.1124/jpet.109.154955
发表时间：
2010-01-01
影响因子：
3.5
作者：
Cervetto, Chiara;Maura, Guido;Marcoli, Manuela
通讯作者：
Marcoli, Manuela
影响因子：
3.2
作者：
Adachi, K;Izumi, M;Mitsuma, T
通讯作者：
Mitsuma, T
影响因子：
4.7
作者：
FAGE, D;VOLTZ, C;CARTER, C
通讯作者：
CARTER, C