The Influence of Age and Sex on: Neuroimmune Function, Cognition and Pain




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The elderly population 65 years and older is rising, and so is the concern to develop targeted geriatric care based on basic and translational research. However, while advances of medicine and technology allow for long-lived lives, they are not necessarily healthier. Low grade chronic inflammation is a predictable outcome of senescence, the process of aging and related impairments, and can facilitate age-associated diseases. It not only accompanies all aged systems, but it allows for a highly reactive immune response in the aged, which can influence other biological functions such as neuroimmune crosstalk. Neurons are easily sensitized following inflammation and can induce an adaptive response such as pain induced by peripheral injury as well as cognitive impairment during infection. However, little is known about how the aged inflammatory phenotype challenges such behaviors, especially in older females. Using a repertoire of behavior, physiology, anatomy and biochemical approaches, this thesis proposes to understand the interaction of age, sex, and neuroimmune function in the context of cognition, pain, and inflammation. Further, it will attempt to identify age-dependent modulation of these behaviors by cap-dependent translation. In the following chapters, I will demonstrate that development of acute peripheral inflammation (edema and temperature) and inflammatory pain (evoked and spontaneous) in the aged are highly dependent on cap-dependent translation while working memory and cytokine production are mostly unaltered by eIF4E phosphorylation. I will emphasize the lack of aging studies addressing sex as a biological variable and will demonstrate that sex can determine the behavioral and inflammatory output in postoperative pain in aging. I further propose future directions that should be addressed in hopes to identify therapeutic interventions for the geriatric population, which focuses on neuron adaptations to heightened inflammation including neurogenic inflammation and neuroplasticity.



Biology, Neuroscience, Health Sciences, Immunology