Aging is a multifactorial process, in which a variety of neurobehavioral functions including social motivation and social recognition abilities decline at different rates, yet very little is known about the neural basis of these deleterious changes. The overarching goal of this proposal is to evaluate the neural mechanism(s) underlying the disintegration of social behavior during the natural course of aging, using rats as a model system. We hypothesize that the gradual decline in social behavior during senescence is symptomatic of both reduced motivational drive toward, and impaired recognition of, social stimuli. We argue that two established consequences of aging - a progressive decline in circulating androgen levels, termed andropause, and a gradual transition of the CNS toward a heightened state of pro-inflammation - play a key role in the disintegration of social behavior during senescence. The proposed mechanism is that gradual loss of circulating androgens leads to disinhibition of pro-inflammatory cytokines such as interleukin-1, which short-circuits the release of oxytocin (OT) expression in the paraventricular nucleus (PVN) of the hypothalamus and release in the medial amygdala (MeA), a key requisite for social motivation/recognition processes. Thus, Specific Aim 1 will characterize the age-related nature of social behavior deficits using a series of social behavior tasks, while at the same time determining the role of OT neurons in the MeA on the degradation of social behavior in aged rats.
Specific Aim 2 will test the impact of the CNS pro-inflammatory state on the blunted response of social behavior circuitry and the therapeutic effect of administration of anti-inflammatory agents in aged rats.
Specific Aim 3 will determine the role of gonadal hormones on the transition of the CNS toward a pro-inflammatory state and its impact on social behavior and their respective mechanisms of action. The outcome of the proposed work will integrate several core features of the aging process (declining androgens, heightened inflammation, altered neuropeptide regulation) into a meaningful mechanistic portrait of how social behavior erodes across the lifespan, and offer several specific therapeutic targets for reversing this process. As a result, the present studies hold great promise for translating findings from rodent models into direct improvements in the quality of life for aging populations.

Public Health Relevance

The natural course of aging is associated with a gradual but profound reduction in social behavior, which jeopardizes the quality of life during late stages of aging. In this proposal, we argue that two consequences of aging, the decline in circulating gonadal hormones and low-grade inflammation, conspire to short-circuit the primary neural pathway that underlies the normal expression of social behavior. The proposed work implicates specific strategies for ameliorating deficits in social behavior during senescence.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Mackiewicz, Miroslaw
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State University of NY, Binghamton
Schools of Arts and Sciences
United States
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Russell, Ashley L; Tasker, Jeffrey G; Lucion, Aldo B et al. (2018) Factors promoting vulnerability to dysregulated stress reactivity and stress-related disease. J Neuroendocrinol 30:e12641
Lovelock, Dennis F; Deak, Terrence (2018) Neuroendocrine and neuroimmune adaptation to Chronic Escalating Distress (CED): A novel model of chronic stress. Neurobiol Stress 9:74-83
Perkins, Amy E; Piazza, Michelle K; Deak, Terrence (2018) Stereological Analysis of Microglia in Aged Male and Female Fischer 344 Rats in Socially Relevant Brain Regions. Neuroscience 377:40-52
Surkin, P N; Brenhouse, H; Deak, T et al. (2018) Stress, alcohol and infection during early development: A brief review of common outcomes and mechanisms. J Neuroendocrinol 30:e12602
Perkins, Amy E; Vore, Andrew S; Lovelock, Dennis et al. (2018) Late aging alters behavioral sensitivity to ethanol in a sex-specific manner in Fischer 344 rats. Pharmacol Biochem Behav 175:1-9
Hamasato, Eduardo Kenji; Lovelock, Dennis; Palermo-Neto, João et al. (2017) Assessment of social behavior directed toward sick partners and its relation to central cytokine expression in rats. Physiol Behav 182:128-136
Gano, Anny; Doremus-Fitzwater, Tamara L; Deak, Terrence (2017) A cross-sectional comparison of ethanol-related cytokine expression in the hippocampus of young and aged Fischer 344 rats. Neurobiol Aging 54:40-53
Deak, Terrence; Kudinova, Anastacia; Lovelock, Dennis F et al. (2017) A multispecies approach for understanding neuroimmune mechanisms of stress. Dialogues Clin Neurosci 19:37-53
Spencer, Robert L; Deak, Terrence (2017) A users guide to HPA axis research. Physiol Behav 178:43-65
Perkins, Amy E; Woodruff, Elizabeth R; Chun, Lauren E et al. (2017) Analysis of c-Fos induction in response to social interaction in male and female Fisher 344 rats. Brain Res 1672:113-121

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