PLASTICITY IN THE AGING OLFACTORY SYSTEM

现在已知嗅觉系统会发生功能改变。 在正常衰老期间，并与老年病相关。朱鹭 提案将检验以下假设：基因的神经可塑性 在老化的哺乳动物嗅觉系统中，表达受到影响。这个 研究将集中在嗅觉的神经再生能力上。 上皮间存在的营养关系以及 感受器上皮和嗅球。在幼年的嗅球里 动物，我们已经证明了儿茶酚胺的表达 生物合成酶酪氨酸羟基酶(TH)，但不是其他 芳香L氨基酸等神经递质生物合成酶 脱羧酶(AADC)和谷氨酸脱羧酶(GAD)， 外周传入性跨神经元调节。拟议中的实验 利用分子生物学技术研究 神经递质特异性基因在衰老啮齿动物和人类中的表达 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在小鼠脑内的表达 小鼠和大鼠的嗅球。嗅觉标记蛋白(OMP)， 成熟的嗅觉感受器细胞及其突起中表达的蛋白质， 将被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 去传入和/或气味剥夺后，尤指以下 幼年、中年和老年动物的可逆性损伤。OMP 表达将监测嗅觉的再生能力 3)与年龄相关的改变将在 将诸如凝集素之类的配体从嗅上皮转移到嗅觉上皮 大脑。还将确定配体的神经毒性作用；4) 神经递质生物合成酶及其mRNAs的分布 将在正常受试者的人类嗅球中进行检查 年龄谱和患有年龄相关障碍的个人，如 阿尔茨海默氏症。拟议的研究可能表明，如果功能 缺陷与年龄相关的再生能力改变有关。 嗅觉上皮的能力和/或嗅觉的能力 球茎植物对干扰做出反应。

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.