Early Life Exercise and Prebiotic Diet Modulate Stress Reactive Neurocircuitry, Increase Stress Resistance, and Promote Adaptive Gut Microorganisms

Mika, Agnieszka Karolina

Graduate Thesis Or Dissertation

Early Life Exercise and Prebiotic Diet Modulate Stress Reactive Neurocircuitry, Increase Stress Resistance, and Promote Adaptive Gut Microorganisms Public Deposited

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Citeable URL: https://scholar.colorado.edu/concern/graduate_thesis_or_dissertations/76537140z

Abstract

Early life is often described as period of vulnerability, as aversive events during this time lead to stress-related psychiatric disorders later in life. We demonstrate that early life is also a period of opportunity, as health promoting manipulations during this time can produce positive mental health outcomes that persist as the organism ages. Exercise is one such positive manipulation. Using a rodent model, we have previously shown that six weeks of habitual exercise on running wheels protects against stress-induced anxiety and depressive-like behavior, and produces numerous neurobiological adaptations. These neural adaptations include plastic changes within the brain’s serotonin circuits, which serve to attenuate stress-induced serotonergic dysregulation responsible for these behaviors. However, when exercise is begun in adulthood, these behavioral and neurobiological effects are short lived, and adults must continue to exercise in order to maintain mental health benefits. Here, we demonstrate that exercise begun earlier, during the developmentally sensitive juvenile period, can produce lasting protection against the behavioral consequences of stress. These effects persist even after wheel access is removed and the organism is no longer physically active, and are paralleled by persistent alterations in gene expression within serotonin circuits. In addition, durations of exercise shorter than those required by adult rats can produce lasting stress resistance. Early life exercise produces robust adaptations in other physiological systems. We also demonstrate that exercise initiated during the juvenile period uniquely modulates gut microbial ecology by increasing bacteria and metabolites previously shown to benefit mental health. Furthermore, sedentary juvenile rats fed diets containing prebiotic fibers—fibers known to increase probiotic gut bacteria— are protected against stress-induced anxiety and depressive-like behavior later in life. Like exercise, early life prebiotic diet produces adaptations within stress- sensitive brain circuits. Moreover, oral antibiotics fed to exercising juvenile rats dampen the ability of exercise to protect against the behavioral consequences of stress. Our work highlights early life as a window of opportunity for lasting stress resistance, and suggests that gut microbes play a role in mediating these effects.

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