PLASTICITY IN THE AGING OLFACTORY SYSTEM

老化嗅觉系统的可塑性

• 批准号: 3121602
• 负责人: Harriet D. Baker
• 金额: $ 16.77万
• 依托单位: WINIFRED MASTERSON BURKE MED RES INST
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-02-01 至 1996-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3121602
• 关键词: Alzheimer's disease; aging; animal old age; aromatic L aminoacid decarboxylase; biological transport; catecholamines; developmental neurobiology; disease /disorder model; enzyme biosynthesis; enzyme mechanism; enzyme substrate; epithelium; gene expression; genetic markers; glutamate decarboxylase; human tissue; hydrolase; intracellular transport; laboratory mouse; laboratory rat; ligands; messenger RNA; neural plasticity; neurogenesis; neurotoxins; neurotransmitter biosynthesis; neurotransmitter receptor; olfactory lobe; transneuronal degeneration; tyrosine analog

Functional alterations are now known to occur in the olfactory system during normal aging and in association with diseases of aging. Ibis proposal will examine the hypothesis that neuroplasticity of gene expression is compromised in the aging mammalian olfactory system. The studies will focus on the neuroregenerative capacity of the olfactory epithelium as well as the trophic relationships which exist between the receptor epithelium and olfactory bulb. In the olfactory bulbs of young animals, we have demonstrated that expression of the catecholamine biosynthetic enzyme tyrosine hydroxylase (TH), but not other neurotransmitter biosynthetic enzymes such as aromatic L-amino acid decarboxylase (AADC) and glutamic acid decarboxylase (GAD), is under peripheral afferent transneuronal regulation. The proposed experiments use molecular biological techniques to investigate neurotransmitter-specific gene expression in the aging rodent and human olfactory systems. 1) Age-associated changes win be determined in the expression of the neurotransmitter enzyme genes, TH, AADC and GAD, in the olfactory bulbs of both mice and rats. Olfactory marker protein (OMP), a protein expressed in mature olfactory receptor cells and their processes, will be assessed to indicate the integrity of olfactory afferent innervation; 2) Plasticity of enzyme gene expression will be assessed following deafferentation and/or odor deprivation, especially following reversible lesions, in young, middle aged and old animals. OMP expression will monitor the regenerative capacity of the olfactory epithelium; 3) Age-related alterations will be investigated in the transport of ligands such as lectins from the olfactory epithelium to the brain. The neurotoxic effects of the ligands also will be determined; 4) The distribution of neurotransmitter biosynthetic enzymes and their mRNAs will be examined in human olfactory bulb from normal subjects spanning the age spectrum and individuals with age-related disorders such as Alzheimer's disease. The proposed studies may indicate if the functional deficits are associated with age-related changes in the regenerative capacity of the olfactory epithelium and/or the ability of the olfactory bulb to respond to perturbation.

现在已知嗅觉系统发生功能改变 在正常衰老过程中以及与衰老疾病相关的过程中。 宜必思酒店 该提案将检验基因的神经可塑性的假设 衰老的哺乳动物嗅觉系统的表达受到损害。 这 研究将集中于嗅觉的神经再生能力 上皮以及之间存在的营养关系 受体上皮和嗅球。 在年轻人的嗅球中 在动物中，我们已经证明儿茶酚胺的表达 生物合成酶酪氨酸羟化酶 (TH)，但不是其他酶 神经递质生物合成酶，例如芳香族L-氨基酸 脱羧酶（AADC）和谷氨酸脱羧酶（GAD），在 外周传入跨神经元调节。 拟议的实验 使用分子生物学技术来研究 衰老啮齿动物和人类的神经递质特异性基因表达 嗅觉系统。 1) 与年龄相关的变化将在 神经递质酶基因 TH、AADC 和 GAD 的表达 小鼠和大鼠的嗅球。 嗅觉标记蛋白（OMP） 成熟嗅觉受体细胞及其过程中表达的蛋白质， 将进行评估以表明嗅觉传入的完整性 神经支配； 2) 评估酶基因表达的可塑性 在传入神经阻滞和/或气味剥夺之后，尤其是在 年轻、中年和老年动物的可逆性损伤。 欧姆普 表达将监测嗅觉的再生能力 上皮； 3) 与年龄相关的改变将在 将凝集素等配体从嗅觉上皮转运至嗅觉上皮 脑。 配体的神经毒性作用也将被确定； 4） 神经递质生物合成酶及其mRNA的分布 将在正常受试者的人类嗅球中进行检查 年龄范围和患有与年龄相关的疾病的个体，例如 阿尔茨海默病。 拟议的研究可能表明功能是否 缺陷与年龄相关的再生能力变化有关 嗅觉上皮细胞的能力和/或嗅觉的能力 灯泡对扰动做出反应。