Regeneration in the olfactory system

嗅觉系统的再生

• 批准号: 8610287
• 负责人: Stuart J Firestein
• 金额: $ 33.65万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8610287
• 关键词: 2 year old; Address; Adult; Afferent Neurons; Age; Aging; Aging-Related Process; Animals; Area; Axon; Biological Assay; Brain Injuries; Cell Aging; Cells; Chemicals; Custom; Data; Development; Diet Habits; Diphtheria Toxin; Dorsal; Elderly; Epithelium; Functional disorder; Gene Expression; Gene Expression Profile; Genetic; Growth; Injection of therapeutic agent; Lesion; Life; Mammals; Mus; Natural regeneration; Nature; Nerve Degeneration; Nerve Regeneration; Nervous system structure; Neurodegenerative Disorders; Neurons; Odorant Receptors; Odors; Olfactory Epithelium; Pathology; Pattern; Peripheral; Population; Positioning Attribute; Process; Quality of life; Receptor Gene; Recovery; Research; Sensory; Specialized Epithelial Cell; Staging; Stem cells; Stimulus; Sum; Synapses; Synaptic Transmission; Synaptic plasticity; System; Testing; Therapeutic; Tissues; aged; cell age; diphtheria toxin receptor; improved; insight; juvenile animal; killings; meetings; molecular marker; neuroepithelium; normal aging; nutrition; olfactory bulb; postnatal; programs; public health relevance; receptor; reconstitution; regenerative; relating to nervous system; research study; response; response to injury; stem cell division; tool; young adult

DESCRIPTION (provided by applicant): The peripheral mammalian olfactory epithelium is a dynamic tissue that contains stem cells capable of generating new sensory neurons in response to injury or pathology. We have recently determined that this regenerative capacity remains robust even in very old animals. This raises several critical questions about the olfactory system and its unique capacity to regenerate neurons. Are these older stem cells capable of generating normal functioning neurons? How do they determine which receptor genes to express, as these differ at different stages of an animal's life? How do these new neurons integrate into an older established tissue and the existing circuitry of the olfactory bulb? We have proposed to use a genetic strategy in which the Diphtheria toxin receptor is expressed specifically in OMP+ mature olfactory sensory neurons. Upon injection of the diphtheria toxin only those cells expressing the receptor will be killed, resulting in a lesion of the OSN population with little or no collateral damage to other cells in the epithelium or in the target olfactory bulb. This allows us to examine the re-growth of a new neuroepithelium in an otherwise normal, but older animal. These experiments will provide insight into the tissue aging process and into the reconstitution of a new olfactory system in aged animals. We hope to gain an understanding of neuronal proliferation that will allow us to imagine ways to compensate for neurodegenerative losses in numerous pathologies and over the course of normal aging. Additionally it may suggest strategies for improving the olfactory sense in the aged, thereby reversing the poor nutrition and quality of life common to this population.

描述（由申请人提供）：外周哺乳动物嗅觉上皮是一种动态组织，其中包含能够响应损伤或病理学而产生新的感觉神经元的干细胞。我们最近确定，即使在非常古老的动物中，这种再生能力也仍然强大。这就提出了有关嗅觉系统及其再生神经元独特能力的几个关键问题。这些较旧的干细胞是否能够产生正常功能的神经元？他们如何确定要表达的受体基因，因为它们在动物生命的不同阶段有所不同？这些新神经元如何集成到较旧的组织和嗅球的现有电路中？我们建议使用一种遗传策略，其中毒素受体在OMP+成熟的嗅觉感觉神经元中特别表达。注射白喉毒素后，只有那些表达受体的细胞将被杀死，从而导致OSN群体的病变，而上皮细胞或目标嗅球中的其他细胞几乎没有或没有附带损害。这使我们能够在原本正常但较老的动物中检查新的神经上皮的重生。这些实验将提供有关组织老化过程的洞察力，并为老年动物的新嗅觉系统的重建。我们希望能够了解神经元增殖，这将使我们能够想象方法可以补偿许多病理和正常衰老过程中的神经退行性损失。此外，它可能会提出改善老年嗅觉意义的策略，从而扭转该人群共有的营养和生活质量差。