Olfactory Function in Schizophrenia: A Lifespan Analysis

描述（由申请人提供）：此修订申请提案旨在就母公司RO1的范围和目标开辟新的领域，该RO1授予为期5年，从2008年3月1日开始。根据《康复法案》的目标和no - od -09- 058号通知，我们计划系统地收集和分析嗅觉上皮活检组织，并对精神分裂症患者和健康对照者的嗅觉系统进行详细的外周和中枢电生理研究。嗅觉上皮的独特之处在于，它构成了可以从活人身上获得的再生神经细胞的唯一来源。也就是说，嗅觉受体神经元在鼻上皮中的位置允许非侵入性地进入活体受试者的这些神经元。这为直接评估患者体内神经元完整性提供了一个独特的机会。来源于人嗅上皮活检的原代培养物随后可用于研究不同条件和疾病状态下个体的神经生物学特征。嗅觉活检组织的收集将允许进一步表征OE基底细胞的超微结构特征以及基因表达谱，以更好地定义每种细胞类型在神经发生中的作用。新的方法将被用于检查嗅觉感觉处理的外围成分，即嗅觉事件相关电位（OERPs），以及更传统的嗅觉诱发电位的头皮记录。我们将研究30名精神分裂症患者和30名无关的健康对照。体内电生理研究的结果将与使用来自同一受试者的ORN组织活检的细胞和分子研究的结果相结合。我们的工作模型是嗅觉缺陷反映了遗传介导的神经元间连接异常，这是由神经发生和突触形成的神经发育障碍过程引起的。宾夕法尼亚大学医学院为当地经济做出了巨大贡献。2008年，宾夕法尼亚大学医学院为该地区创造了37,000个工作岗位和54亿美元的经济活动，该地区训练有素的劳动力为840个宾夕法尼亚大学的研究职位提供了超过24,600份申请。目前的提案将创造或保留2.5个工作岗位。

DESCRIPTION (provided by applicant): This Revision Application proposal seeks to break new ground in regard to the scope and aims of the parent RO1, which was awarded for 5 years beginning 03/01/08. Consistent with the goals of the Recovery Act and notice NOT-OD-09- 058, we plan to systematically collect and analyze olfactory epithelial biopsy tissue as well as perform detailed peripheral and central electrophysiological studies of the olfactory system in schizophrenia patients and healthy controls. Olfactory epithelium is unique in that it constitutes the sole source of regenerating neural cells that can be obtained from a living human. That is, the location of olfactory receptor neurons in the nasal epithelium allows noninvasive access to these neurons in living subjects. This offers a unique opportunity to directly assess neuronal integrity in vivo in patients. Primary cultures derived from human olfactory epithelial biopsies can subsequently be utilized to study neurobiological characteristics of individuals under different conditions and disease states. The collection of olfactory biopsy tissue will allow for further characterization of basal cells in OE in terms of their ultrastructural features as well as gene expression profiling to better define the role of each cell type in neurogenesis. New methodologies will be employed to examine peripheral components of olfactory sensory processing, i.e., olfactory event-related potentials (OERPs), as well as more traditional scalp recordings of the olfactory- evoked potential. We will study 30 schizophrenia patients and 30 unrelated healthy controls. Results from the in vivo electrophysiological studies will be integrated with the results of the cellular and molecular studies that use ORN tissue biopsies obtained from the same subjects. Our working model is that olfactory deficits reflect genetically-mediated abnormalities in neuron-to-neuron connectivity, arising from neurodevelopmentally disturbed processes of neurogenesis and synapse formation. Penn Medicine contributes substantially to the local economy. In 2008, Penn Medicine created 37,000 jobs and $5.4 billion in regional economic activity, with the area's highly trained workforce producing more than 24,600 applications for just 840 open Penn staff research positions. The current proposal will create or retain 2.5 jobs. PUBLIC HEALTH RELEVANCE: Schizophrenia is currently thought to be a complex genetic disorder, with altered neuronal development, perhaps very early in life, important in determining vulnerability. Neurogenesis and neurodevelopment occur in the adult olfactory epithelium (OE), and the collection and study of olfactory biopsy tissue may provide insights into the neuro- biological basis of altered neurodevelopment in this disorder. We plan to collect and analyze OE biopsy tissue as well as perform detailed peripheral and central electrophysiological studies of the olfactory system in schizophrenia patients and healthy controls. Penn Medicine contributes substantially to the local economy. In 2008, Penn Medicine created 37,000 jobs and $5.4 billion in regional economic activity, with the area's highly trained workforce producing more than 24,600 applications for just 840 open Penn staff research positions. The current proposal will create or retain 2.5 jobs.