title: The exercise-glucocorticoid paradox: How exercise is beneficial to cognition, mood, and the brain while increasing glucocorticoid levels.
abstract: Exercise is known to have beneficial effects on cognition, mood, and the brain. However, exercise also activates the hypothalamic-pituitary-adrenal axis and increases levels of the glucocorticoid cortisol (CORT). CORT, also known as the "stress hormone," is considered a mediator between chronic stress and depression and to link various cognitive deficits. Here, we review the evidence that shows that while both chronic stress and exercise elevate basal CORT levels leading to increased secretion of CORT, the former is detrimental to cognition/memory, mood/stress coping, and brain plasticity, while the latter is beneficial. We propose three preliminary answers to the exercise-CORT paradox. Importantly, the elevated CORT, through glucocorticoid receptors, functions to elevate dopamine in the medial prefrontal cortex under chronic exercise but not chronic stress, and the medial prefrontal dopamine is essential for active coping. Future inquiries may provide further insights to promote our understanding of this paradox.
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Chong
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. Electronic address: snakaga@med.hokudai.ac.jp.
authors.forename: Shin
authors.initials: S
authors.lastname: Nakagawa
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Yan
authors.initials: Y
authors.lastname: An
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Ito
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kitaichi
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kusumi
mesh_terms: D000339:Affect / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000502:physiology*; D003071:Cognition / Q000502:physiology*; D015444:Exercise / Q000502:physiology*; D005938:Glucocorticoids / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid
keywords: Brain plasticity; Chronic stress; Corticosterone; Cortisol; Depression; Dopamine; Exercise; Glucocorticoid receptor; Medial prefrontal cortex; Wheel running