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, a, and two regulatory subunits, and ?. 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 AMPKa 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 AMPK?1/?2 genetically null astrocytes in autophagy and apoptosis.
The mammalian brain depends on a constant supply of glucose and oxygen. Lack of either one of them rapidly leads to failure of neuronal function. The regulation of brain energy metabolism is accomplished via the constant communication between astrocytes and neurons. Furthermore, the role of astrocytes in stroke and neurodegenerative processes is also becoming increasingly appreciated. Many of these neurological diseases have been implicated to be due to dysregulation of autophagy and energy metabolism. Model organism studies have shown that AMP-activated protein kinase (AMPK) function is critical for neuronal maintenance. Lack of AMPK function results in progressive neurodegeneration, which has implications for many neurodegenerative diseases including Alzheimer's and Parkinson's. Additionally, Ghrelin, an AMPK activator, has also been shown to play a role in various neurodegenerative processes, including AD, and Parkinson's. Furthermore, Metformin is a widely used Type 2 diabetes drug shown to have its therapeutic effects through the activation of AMPK. Furthermore, rapamycin has been shown to be a potential therapeutic modulator for many neurodegenerative disorders, such as Alzheimer's, Parkinson's, and Huntington's.
