Senescence, neurodegeneration, and sensory/motor decline in a social invertebrate

描述（由申请人提供）：人口老龄化带来了重大的社会和健康挑战。在衰老的分子和社会方面的研究中，特别重要的是实现对作为正常衰老和疾病的一部分发生的行为和神经生物学过程的全面理解。一种社会无脊椎动物衰老模型的发展，蚁齿，在衰老分析中具有多重优势。1. 与人类一样，蚂蚁高度依赖社会互动，我们可以通过实验操纵蚂蚁的社会环境来快速评估其对衰老的分子、神经和行为方面的影响；2. 齿形果蝇是社会生物学中的“果蝇”，在了解该物种的行为和神经生物学发育方面取得了重大进展；和3。工蚁在羽化后的20天内进行行为发育，它们的寿命只有四个半月，这使它们成为在加速的时间框架内探索神经退化和认知衰退模式的有用模型。我们新的衰老社会模型的发展将阐明社会互动如何介导神经和行为衰退，并确定血清素是否可以挽救衰老表型，血清素在蚂蚁的行为成熟和患有神经退行性疾病的人类的认知功能中发挥重要作用。拟议的研究根据社会背景，检查是否与年龄相关的行为下降是由神经退行性细胞死亡和/或脑血清素的变化介导的。我们预测：1)老年职工的行为效能会下降。2)脑细胞凋亡在行为发育过程中呈高水平，随年龄增长而下降；3)血清素水平在衰老个体中下降，在缺乏社会环境的个体中下降得更快。此外，使用5 -羟色胺前体和抑制剂对脑5 -羟色胺的药理学改变将决定5 -羟色胺是否足以挽救行为衰退。我们的发现将扩大我们对年龄相关行为和衰老之间关系的理解，并研究社会性和神经调节剂如何减轻神经变性和衰老的感觉和运动后果。我们有三个具体的目标：具体目标1：通过量化嗅觉敏感性和运动表现来表征牙齿牙鼠工蚁衰老相关的行为变化。特异性目的2：免疫组织化学定位和量化神经元凋亡。具体目的3：通过HPLC分析和药物治疗，确定血清素是否可以挽救社会环境中与年龄相关的感觉和运动功能衰退。

DESCRIPTION (provided by applicant): The aging population poses significant social and health challenges. Of particular importance in the study of molecular and social aspects of senescence is achieving a comprehensive understanding of behavioral and neurobiological processes that occur as part of both normal aging and disease. The development of a social invertebrate model of aging, the ant Pheidole dentata, presents multiple advantages in the analysis of aging. 1. Like humans, ants are highly dependent on social interactions, and we can experimentally manipulate the social environment in ants to rapidly assess its influence on molecular, neural and behavioral aspects of aging; 2. Research on P. dentata, the "fruit fly" of sociobiology, has yielded significant progress in understanding behavioral and neurobiological development in this species; and 3. Workers undergo behavioral development within 20 days of eclosion and have a lifespan of only four and a half months, making them useful models to explore patterns of neurodegeneration and cognitive decline within an accelerated timeframe. The development of our new social model of aging will illuminate how social interactions mediate neural and behavioral decline and determine if serotonin, which is significant in behavioral maturation in ants and cognitive functioning in humans afflicted with neurodegenerative disease, can rescue aging phenotypes. The proposed research examines if age-associated behavioral decline is mediated by neurodegenerative cell death and/or changes in brain serotonin according to social context. We predict: 1) Behavioral efficacy will decline in old-age workers. 2) Brain apoptosis will be high throughout behavioral development and decline with increasing age; and 3) Serotonin levels will decrease in senescing individuals and will decline more rapidly in individuals in a deprived social environment. Furthermore, pharmacological alteration of brain serotonin using both a serotonin precursor and inhibitor will determine if serotonin is sufficient to rescue behavioral decline. Our findings will expand our understanding of the relationship between age-related behavior and senescence, and examine how sociality and neuromodulators may mitigate the sensory and motor consequences of neurodegeneration and aging. We have three specific aims: Specific Aim 1: To characterize senescence-associated behavioral changes by quantifying olfactory sensitivity and motor performance in P. dentata workers. Specific Aim 2: To immunohistochemically localize and quantify neuronal apoptosis. Specific Aim 3: To determine whether serotonin can rescue age-related decline in sensory and motor function in a social context by HPLC analysis and pharmacological treatments. PUBLIC HEALTH RELEVANCE: Human aging is influenced by social interactions. We have developed a novel insect model system to examine how social behavior and the neurotransmitter serotonin may regulate age-related declines in behavior. The common occurrence of serotonin and great similarity in molecular events of neurodegeneration in insects and humans allows us to efficiently examine the effect of brain chemistry and the social environment on cognitive decline and neural processes through experimental manipulation.