Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors.

https://scholarworks.smith.edu/cgi/viewcontent.cgi?article=1011&context=nsc_facpubs

Stress, social behavior, and resilience: insights from rodents.

Glucocorticoids released from the adrenal gland in response to stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis induce activity in the cellular reduction-oxidation (redox) system. The redox system is a ubiquitous chemical mechanism allowing the transfer of electrons between donor/acceptors and target molecules during oxidative phosphorylation while simultaneously maintaining the overall cellular environment in a reduced state. The objective of this review is to present an overview of the current literature discussing the link between HPA axis-derived glucocorticoids and increased oxidative stress, particularly focussing on the redox changes observed in the hippocampus following glucocorticoid exposure.

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Activation of the hypothalamic-pituitary-adrenal stress axis induces cellular oxidative stress

Adult neurogenesis: a substrate for experience-dependent change

Air pollution is a risk factor for cardiovascular and respiratory morbidity and mortality. A growing literature also links exposure to diverse air pollutants (e.g., nanoparticles, particulate matter, ozone, traffic-related air pollution) with brain health, including increased incidence of neurological and psychiatric disorders such as cognitive decline, dementia (including Alzheimer's disease), anxiety, depression, and suicide. A critical gap in our understanding of adverse impacts of pollutants on the central nervous system (CNS) is the early initiating events triggered by pollutant inhalation that contribute to disease progression. Recent experimental evidence has shown that particulate matter and ozone, two common pollutants with differing characteristics and reactivity, can activate the hypothalamic-pituitary-adrenal (HPA) axis and release glucocorticoid stress hormones (cortisol in humans, corticosterone in rodents) as part of a neuroendocrine stress response. The brain is highly sensitive to stress: stress hormones affect cognition and mental health, and chronic stress can produce profound biochemical and structural changes in the brain. Chronic activation and/or dysfunction of the HPA axis also increases the burden on physiological stress response systems, conceptualized as allostatic load, and is a common pathway implicated in many diseases. The present paper provides an overview of how systemic stress-dependent biological responses common to particulate matter and ozone may provide insight into early CNS effects of pollutants, including links with oxidative, inflammatory, and metabolic processes. Evidence of pollutant effect modification by non-chemical stressors (e.g., socioeconomic position, psychosocial, noise), age (prenatal to elderly), and sex will also be reviewed in the context of susceptibility across the lifespan.

/pdf/air-pollution-stress-and-allostatic-load-linking-systemic-4cv1xq5q1y.pdf

Air Pollution, Stress, and Allostatic Load: Linking Systemic and Central Nervous System Impacts.

Stress can exert long-lasting changes on the brain that contribute to vulnerability to mental illness, yet mechanisms underlying this long-term vulnerability are not well understood. We hypothesized that stress may alter the production of oligodendrocytes in the adult brain, providing a cellular and structural basis for stress-related disorders. We found that immobilization stress decreased neurogenesis and increased oligodendrogenesis in the dentate gyrus (DG) of the adult rat hippocampus and that injections of the rat glucocorticoid stress hormone corticosterone (cort) were sufficient to replicate this effect. The DG contains a unique population of multipotent neural stem cells (NSCs) that give rise to adult newborn neurons, but oligodendrogenic potential has not been demonstrated in vivo. We used a nestin-CreER/YFP transgenic mouse line for lineage tracing and found that cort induces oligodendrogenesis from nestin-expressing NSCs in vivo. Using hippocampal NSCs cultured in vitro, we further showed that exposure to cort induced a pro-oligodendrogenic transcriptional program and resulted in an increase in oligodendrogenesis and decrease in neurogenesis, which was prevented by genetic blockade of glucocorticoid receptor (GR). Together, these results suggest a novel model in which stress may alter hippocampal function by promoting oligodendrogenesis, thereby altering the cellular composition and white matter structure.

/pdf/stress-and-glucocorticoids-promote-oligodendrogenesis-in-the-1lg3fe33zg.pdf

Christian Mirescu

Papers

Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus