Genetic Analysis of AMPK-alpha in Astrocytes during Normal and Energetic Stress

摘要 学术研究促进奖（AREA）旨在促进主要在以下领域的研究 本科院校（PUI）-（R15）将极大地影响我的职业目标和我的 本科生和完全符合这个奖项的预期目的。具体而言，该奖项 1）允许我继续对新陈代谢感兴趣，因为它与正常和 患病的大脑，2）让学生接触相关的研究，3）支持Trinity的承诺 大学有科学研究和发现。在此期间，我实验室的学生将 提供了一个特殊的机会，以获得培训领域的小鼠遗传学，皮质 开发和培养初级神经元以及星形胶质细胞，这将提高他们对 分子和细胞神经科学。作为一名年轻的教师，这个奖项将积极影响 实现我的长期目标。作为一名新的助理教授，获得一个有声望的奖项将 作为一名神经生物学研究人员和教授，在启动成功的职业生涯轨迹方面发挥关键作用。 PUI。 我的建议集中在神经系统中的AMPK。AMPK是一种三聚体， 催化亚基α和两个调节亚基β和γ。作为能量传感器和调节器， 由于AMPK在神经元代谢中起重要作用，因此预计AMPK将在神经元发育过程中发挥重要作用， 维护和生存。然而，到目前为止，AMPKα功能的遗传分析在 哺乳动物的神经系统尚未被探索。因此，本建议旨在确定 AMP激活的蛋白激酶可能在哺乳动物神经系统中发挥作用的分子机制。 我们将专门评估AMPKα1/α2基因缺失的星形胶质细胞在体外自噬中的作用 和凋亡

Abstract An Academic Research Enhancement Award (AREA) award to promote research at primarily undergraduate institutions (PUIs) –(R15) will greatly impact both my career goals and my undergraduate students and fully meet the intended purpose of this award. Specifically, this award would 1) allow me to pursue my continuing interest in metabolism as it relates to the normal and diseased brain, 2) expose students to relevant research, and 3) support the commitment Trinity University has for scientific research and discovery. During this award period students in my lab will be afforded an exceptional opportunity to obtain training in the field of mouse genetics, cortical development and culturing primary neurons as well as astrocytes, which will enhance their interest in molecular and cellular neuroscience. As a junior faculty member, this award will positively impact the achievement of my long term goals. As a new assistant professor, securing a prestigious award will be pivotal in launching a successful career trajectory as a neurobiology researcher and professor at a PUI. My proposal focuses on AMPK in the nervous system. AMPK is a trimer composed of a catalytic subunit, α, and two regulatory subunits, β and γ. As an energy sensor and regulator of metabolism, AMPK would be expected to play a vital function during neuronal development, maintenance, and survival. However, to date the genetic analysis of AMPKα function in the mammalian nervous system has not been explored. Therefore, this proposal aims to identify molecular mechanisms AMP-activated protein kinase may play in the mammalian nervous system. We will specifically evaluate the in vitro effects of AMPKα1/α2 genetically null astrocytes in autophagy and apoptosis