New Horizons in Adult Neurogenesis

成人神经发生的新视野

• 批准号: 7299292
• 负责人: AMELIA J EISCH
• 金额: $ 8.96万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7299292
• 关键词: Acute; Adult; Affect; Amelia; Applications Grants; Arts; Award; Biochemical; Biological Assay; Brain; Brain-Derived Neurotrophic Factor; Cell Aging; Cell Cycle; Cell Cycle Progression; Cell Cycle Proteins; Cell Separation; Cells; Chronic; Cognitive deficits; Collaborations; Complex; Comprehension; Data; Doctor of Philosophy; Educational process of instructing; Environment; Exposure to; Faculty; Foundations; Funding; Future; Genes; Genetic Transcription; Green Fluorescent Proteins; Growth Factor; Health; Heroin; Hippocampus (Brain); IL1R1 gene; Immunohistochemistry; In Vitro; Independent Scientist Award; Laboratories; Learning; Light; Medical; Medical center; Mentors; Microarray Analysis; Mitosis; Morphine; Morphine Abuse; Mus; National Institute of Drug Abuse; National Institute of Mental Health; Neuronal Plasticity; Neurons; Numbers; Opiates; Opioid Receptor; Pharmaceutical Preparations; Play; Postdoctoral Fellow; Process; Production; Proliferating; Proteins; Psychiatry; Publications; Rattus; Relapse; Research; Retroviridae; Role; Self-Administered; Series; Signal Transduction; Social Problems; Source; Stem cells; Structure; Students; Techniques; Testing; Time; Transcript; United States; Work; addiction; base; career; cell age; cytokine; dentate gyrus; drug of abuse; improved; in vivo; injured; insight; laser capture microdissection; mouse model; mu opioid receptors; nerve stem cell; nestin protein; neurogenesis; professor; programs; protein expression; receptor; relating to nervous system; repaired

DESCRIPTION (provided by applicant): This is an application for a NIDA Independent Scientist Award (K02). The candidate, Amelia J. Eisch, Ph.D., is an Assistant Professor in her sixth year on the psychiatry faculty at UT Southwestern Medical Center in Dallas. Throughout her career, Dr. Eisch has established a strong record of publications (39 total; 17 from her independent laboratory), awards and funding from both federal (4 from NIDA, 1 from NIA, 1 from NIMH, 1 from NSF) and non-federal (2 from NARSAD, 2 from Stanley Foundation) sources, and mentoring. Since joining the UT Southwestern faculty in 2000, Dr. Eisch has developed a unique research program with a focus on understanding mechanisms underlying the potent negative impact of drugs of abuse on the hippocampus, particularly on adult hippocampal neurogenesis. However, increasing administrative and teaching obligations have hampered Dr. Eisch's research progress, such that she is able to only devote 50% of her time on research. The receipt of a K02 award would remove or restrict these obligations, thus allowing Dr. Eisch (1) to advance her work on the impact of opiates on adult hippocampal neurogenesis; (2) to nurture a newly-developed collaboration on the role of Cdk5 in adult hippocampal neurogenesis; (3) to learn the principals and practice of cutting-edge techniques (fluorescent activated cell sorting, microarray analysis, laser capture microdissection, retrovirus production, and biochemical and neurosphere assays) from UT Southwestern colleagues, and apply them to her research; (4) to use her newly-developed nestin-CreER12 mouse model to its maximum potential for elucidating the impact of drugs of abuse on hippocampal structure; (5) to generate sufficient data for a series of grant applications, and the time to prepare them: a competitive renewal application for her existing R01, a new NIDA R01 application, and an additional small or exploratory grant application, also to NIDA; (5) to spend more time mentoring and interacting with the six graduate students and two postdoctoral fellows in her laboratory; and (6) to engage collaborators from both inside and outside the addiction field in research on hippocampal neuroplasticity induced by drugs of abuse. The stability and protected time offered by this K02 award would ultimately support two new projects exploring the complex relationship between drugs of abuse, adult neural stem cells, and the hippocampal environment in which these cells proliferate. As such, these studies hold great potential to improve our understanding of the complex mechanisms by which drugs of abuse affect brain function, and therefore may open new avenues for treatment of addiction and relapse to drug seeking. These studies will also shed much-needed light on how adult neural stem cells adapt to chronic exposure of a drug of abuse, and thus will be important to future efforts to harness neural stem cells for repair of the injured, even addicted, brain.

描述（由申请人提供）：这是一份 NIDA 独立科学家奖 (K02) 的申请。这位候选人是阿米莉亚·J·艾施博士，她是达拉斯德州大学西南医学中心精神病学系的助理教授，今年已是第六年。在她的整个职业生涯中，Eisch 博士在出版物（总共 39 篇；17 篇来自她的独立实验室）、来自联邦（4 篇来自 NIDA、1 篇来自 NIA、1 篇来自 NIMH、1 篇来自 NSF）和非联邦（2 篇来自 NARSAD、2 篇来自斯坦利基金会）和指导方面的奖项和资助方面建立了良好的记录。自 2000 年加入 UT 西南大学以来，Eisch 博士开发了一项独特的研究项目，重点是了解滥用药物对海马体，特别是成人海马体神经发生的潜在负面影响的机制。然而，日益增加的行政和教学义务阻碍了Eisch博士的研究进展，她只能投入50%的时间进行研究。获得 K02 奖将消除或限制这些义务，从而使 Eisch 博士 (1) 能够推进她关于阿片类药物对成人海马神经发生影响的工作； (2) 就 Cdk5 在成人海马神经发生中的作用培育新的合作； （3）向UT Southwestern同事学习尖端技术（荧光激活细胞分选、微阵列分析、激光捕获显微切割、逆转录病毒生产、生化和神经球测定）的原理和实践，并将其应用到她的研究中； (4) 利用她新开发的 nestin-CreER12 小鼠模型最大程度地阐明滥用药物对海马结构的影响； (5) 为一系列赠款申请生成足够的数据，以及准备这些申请的时间：针对现有 R01 的竞争性更新申请、新的 NIDA R01 申请以及同样向 NIDA 提交的额外小额或探索性赠款申请； （5）花更多的时间与实验室的六名研究生和两名博士后进行指导和互动； (6) 吸引成瘾领域内外的合作者参与滥用药物引起的海马神经可塑性的研究。 K02 奖项提供的稳定性和保护时间最终将支持两个新项目，探索滥用药物、成体神经干细胞以及这些细胞增殖的海马环境之间的复杂关系。因此，这些研究具有巨大的潜力，可以提高我们对滥用药物影响大脑功能的复杂机制的理解，因此可能为治疗成瘾和吸毒复发开辟新途径。这些研究还将揭示成体神经干细胞如何适应长期暴露于滥用药物的情况，因此对于未来利用神经干细胞修复受伤甚至成瘾的大脑的努力非常重要。