RA Receptors and Neurogenesis in the Postnatal Olfactory Epithelium

出生后嗅上皮中的 RA 受体和神经发生

• 批准号: 7284957
• 负责人: MARY ANN ASSON-BATRES
• 金额: $ 21.38万
• 依托单位: TENNESSEE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7284957
• 关键词: Address; Adult; Animals; Anterior; Antibodies; Antigens; Apoptosis; Area; Basal Cell; Binding; Breeding; Cancer Detection; Cell Proliferation; Cells; Complex; Condition; Data; Detection; Development; Embryo; Enzymes; Epithelium; Esterification; Esters; Gene Silencing; Genes; Genetic Transcription; Glycine decarboxylase; Growth; Growth and Development function; Histocompatibility Testing; Human; Knockout Mice; Laboratories; LacZ Genes; Localized; Mediating; Mus; Natural regeneration; Neurons; Normal tissue morphology; Nuclear; Nuclear Receptors; Numbers; Olfactory Epithelium; Olfactory tract; Organ; Outcome; Pathology; Pathology, Other; Pattern; Phenotype; Photoreceptors; Principal Investigator; Process; RXR; Rattus; Reporter; Reporting; Research; Role; Signal Transduction; Site; Source; Supplementation; System; Testing; Tissues; Vitamin A; Vitamin A Deficiency; Work; clinical application; expectation; genetic manipulation; immunoreactivity; in vivo; lecithin-retinol acyltransferase; neurogenesis; olfactory bulb; postnatal; protein protein interaction; receptor; response; spatiotemporal

The essential role of vitamin A (VA) in growth and development is undisputed, but mechanisms underlying its effects have not been fully elucidated. Available data indicate that VA influences growth at the level of cell proliferation, differentiation, maturation, and/or apoptosis through the actions of its oxidative derivative, RA, which binds to and activates nuclear receptor complexes that, in turn, regulate the transcription of genes that impact growth. VA-deficiency disrupts growth and tissue specification processes, which presumably occur due to a reduction in RA availability at the cellular level,. This interpretation is supported by (a) studies showing that supplementation of VA-deficient systems with RA rescues the pathology when the system has the capacity to generate new cells, for example, embryos, but does not rescue the system if it is incapable of generating new cells, for example, photoreceptor cells in adult rats, and (b) studies showing that supplementation of VA-sufficient systems with excess RA causes growth-related deformations and structural duplications. While VA likely has pleiotropic effects on complex animal systems, it is nonetheless reasonable to conclude that among its primary functions is its role as a source of RA for RA-mediated tissue morphogenetic and cell development processes. Consistent with this expectation, the principal investigator has shown that RA is present in VA-sufficient postnatal rat olfactory tissue and is below the level of detection in VA-deficient olfactory tissue, and this decreased availability of RA is accompanied by increased basal cell proliferation and decreased numbers of mature olfactory neurons in the olfactory epithelium (OE). These results lend support to the working hypothesis that RA signaling mediates neurogenesis in vivo. To further elucidate the role of VA status and/or RA signaling in effecting neuron development in vivo, the PI proposes to localize expression of nuclear receptors in the postnatal olfactory organ, localize RA sensitive sites in the olfactory organ, and study the effects of VA in mice whose VA status is compromised either through dietary or genetic manipulation.

维生素 A (VA) 在生长和发育中的重要作用是无可争议的，但其机制 其潜在影响尚未完全阐明。现有数据表明 VA 影响 细胞增殖、分化、成熟和/或凋亡水平上的生长 其氧化衍生物 RA 的作用，它结合并激活核受体复合物， 反过来，调节影响生长的基因的转录。 VA 缺乏会扰乱生长并 组织规范过程，这可能是由于 RA 可用性的减少而发生 细胞水平，。这一解释得到 (a) 研究的支持，该研究表明补充 当系统有能力产生 VA 时，具有 RA 的 VA 缺陷系统可以挽救病理学 新细胞，例如胚胎，但如果系统无法产生新细胞，则无法拯救系统 细胞，例如成年大鼠的感光细胞，以及 (b) 研究表明补充 VA 充足且 RA 过多的系统会导致与生长相关的变形和结构 重复。虽然 VA 可能对复杂的动物系统具有多效性作用，但它仍然 可以合理地得出这样的结论：其主要功能之一是其作为 RA 介导的 RA 来源的作用 组织形态发生和细胞发育过程。与这一预期一致的是，校长 研究人员表明，RA 存在于 VA 充足的出生后大鼠嗅觉组织中，并且低于 缺乏 VA 的嗅觉组织中的检测水平，以及 RA 可用性的降低 伴随基底细胞增殖增加和成熟嗅觉细胞数量减少 嗅觉上皮 (OE) 中的神经元。这些结果支持了以下工作假设： RA 信号介导体内神经发生。进一步阐明 VA 状态和/或 RA 的作用 信号传导影响体内神经元发育，PI建议定位核表达 出生后嗅觉器官中的受体，定位嗅觉器官中的 RA 敏感位点，并研究 VA 对 VA 状态因饮食或遗传而受损的小鼠的影响 操纵。