Involvement of Stat3 in mouse brain development and sexual dimorphism: a proteomics approach.
Involvement of Stat3 in mouse brain development and sexual dimorphism: a proteomics approach.
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DOI：
10.1016/j.brainres.2010.09.074
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发表时间：
2010-11-29
期刊：
影响因子：
2.9
通讯作者：
Butterfield DA
中科院分区：
文献类型：
--
作者：
Di Domenico F;Casalena G;Sultana R;Cai J;Pierce WM;Perluigi M;Cini C;Baracca A;Solaini G;Lenaz G;Jia J;Dziennis S;Murphy SJ;Alkayed NJ;Butterfield DA
虽然STAT3在细胞生理学和组织发育中的作用已被大量研究，但其参与神经组织的发育和维持以及神经保护机制尚不清楚。潜在的广泛的STAT3活动提出了组织和性别特异性作为公认的调节机制的问题。为了探索STAT3在大脑中的功能以及STAT3的性别相关调节的假设，我们分析了神经元特异性STAT3敲除小鼠模型，研究了在没有神经损伤的情况下，STAT3活性对男性和女性脑蛋白表达模式的影响。我们进行了一项蛋白质组学研究，旨在揭示STAT3直接或间接控制的分子通路，强调其在大脑发育和维持中的作用。我们确定了几种蛋白质，属于不同的神经元通路，如能量代谢或突触传递，由STAT3控制，证实了其在大脑发育和维持中的关键作用。此外，我们调查了不同的过程，可能有助于观察到的神经和精神疾病的发病率的性二态行为。有趣的是，STAT3 KO和性别因素都影响几种线粒体蛋白的表达，从而赋予线粒体活性在脑生理调节中的高度重要性和作为治疗靶点的可能相关性。
Although the role of STAT3 in cell physiology and tissue development has been largely investigated, its involvement in the development and maintenance of nervous tissue and in the mechanisms of neuroprotection is not yet known. The potentially wide range of STAT3 activities raise the question of tissue- and gender-specificity as putative mechanisms of regulation. To explore the function of STAT3 in the brain and the hypothesis of a gender-linked modulation of STAT3, we analyzed a neuron-specific STAT3 knockout mouse model investigating the influence of STAT3 activity in brain protein expression pattern in both males and females in the absence of neurological insult. We performed a proteomic study aimed to reveal the molecular pathways directly or indirectly controlled by STAT3 underscoring its role in brain development and maintenance. We identified several proteins, belonging to different neuronal pathways such as energy metabolism or synaptic transmission, controlled by STAT3 that confirm its crucial role in brain development and maintenance. Moreover, we investigated the different processes that could contribute to the sexual dimorphic behavior observed in the incidence of neurological and mental disease. Interestingly both STAT3 KO and gender factors influence the expression of several mitochondrial proteins conferring to mitochondrial activity high importance in the regulation of brain physiology and conceivable relevance as therapeutic target.
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