Severe Life Stress and Oxidative Stress in the Brain: From Animal Models to Human Pathology

Abstract

Significance: Severe life stress (SLS), as opposed to trivial everyday stress, is defined as a serious psychosocial event with the potential of causing an impacting psychological traumatism. Recent Advances: Numerous studies have attempted to understand how the central nervous system (CNS) responds to SLS. This response includes a variety of morphological and neurochemical modifications; among them, oxidative stress is almost invariably observed. Oxidative stress is defined as disequilibrium between oxidant generation and the antioxidant response. Critical Issues: In this review, we discuss how SLS leads to oxidative stress in the CNS, and how the latter impacts pathophysiological outcomes. We also critically discuss experimental methods that measure oxidative stress in the CNS. The review covers animal models and human observations. Animal models of SLS include sleep deprivation, maternal separation, and social isolation in rodents, and the establishment of hierarchy in non-human primates. In humans, SLS, which is caused by traumatic events such as child abuse, war, and divorce, is also accompanied by oxidative stress in the CNS. Future Directions: The outcome of SLS in humans ranges from resilience, over post-traumatic stress disorder, to development of chronic mental disorders. Defining the sources of oxidative stress in SLS might in the long run provide new therapeutic avenues.

New Insights onNOXEnzymes in the Central Nervous System

“…In another animal model of psychosis, induced by social isolation of adolescent rats, both behavioral abnormalities and neurochemical alterations (including high glutamate and loss of parvalbuminpositive neurons) were prevented by apocynin treatment and-importantly-in rats with a loss-of-function mutation in an NOX2 subunit (145,147). There are also indications that severe life stress (possibly contributing to psychosis) leads to oxidative stress in the CNS of humans (146). Further studies will be necessary to understand the relative importance of the NOX/ROS axis in human psychotic disease.…”

Effect of animal mixing as a stressor on biomarkers of autophagy and oxidative stress during pig muscle maturation

“…Stress is a general term that describes the inadequate physiological response of an organism to any mental, emotional or physical demand, whether real or imagined (Schiavone et al, 2013). The cellular mechanisms that trigger stress are unknown, but a relationship between stressors and oxidative stress has been described, because oxidative changes occur in situations such as road transport, weaning or heat stress (Burke et al, 2010).…”

Childhood Trauma and Resilience: Vulnerabilities to Develop Crack/Cocaine Dependence

“…At the same time that traumatic events increase vulnerability to experimentation of psychoactive substances, drug use creates an environment that facilitates the onset of the aforementioned events, which can also affect brain structures and function. When trauma takes place during early development, it becomes a risk factor for the onset of a wide range of psychological manifestations such as major depression, anxiety, eating disorders, bipolar disorder and substance abuse [11,12]. Moreover, individuals with severe drug abuse and PTSD have an increased risk of relapse, and often these substances are used for self-medication, especially because during abstinence trauma reliving symptoms could be increased [13].…”