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

Boston University (Charles River Campus), Boston MA

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Abstract

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.