Chronic stress, cortical plasticity and neuroecology

2010

Weiyang Xiong Stress and the Brain How does stress affect our brain? We all experience stress in our daily lives. When we encounter stressors, our brain's chemical elements will change, in turn affecting the brain's stress response systems. When stress places one's body in a precarious state in which one cannot function properly, one would become extremely vulnerable to disease and illness (Fricchione, 30). The harmful effects of stress could be mitigated if one were to have sufficient external support from family and friends or internal coping mechanisms generated through meditation, healthy diet and regular exercises. In the face of distressing psychological and social stressors, one must expend tremendous energy through one's brain and body to stabilize one's physiologies. Failure to quickly adapt and cope with stressors would result in the impairment of one's brain regions including the hippocampus and the amygdala, leading to severe diseases such as Type II diabetes, depression and PTSD. In order to gain a better understanding of the effects of stressors on different brain regions, one needs to delve deeper into the functions of various brain areas and different roles they play in stress. One's brain plays an active role in maintaining physiological stability "in the face of changing circumstances" in a process called allostasis, the active process of responding to challenges to, and adaptive changes by, an individual (McEwen, 2). The brain adjusts one's stress response systems to accommodate to the increasing demand imposed upon by stress. When the stress becomes too overwhelming or enduring, the brain would find it extremely difficult to maintain energy balance, placing one's health and wellness in jeopardy. Therefore, in the face of severe stressors, the brain's stress response systems notify one's body organs of perceived challenges and threats so the body would have time to react. This system works well under short or acute stress; under chronic stress, however, the brain's depletion in resources would prevent it from meeting the energy demand necessary to adjust the stress 1

Nat Rev Neurosci, 2009

Every day, parents observe the growing behavioural repertoires of their infants and young children, and the corresponding changes in cognitive and emotional functions. These changes are thought to relate to normal brain development, particularly the development of the hippocampus, the amygdala and the frontal lobes, and the complex circuitry that connects these brain regions. At the other end of the age spectrum, we observe changes in cognition that accompany aging in our parents. These changes are related to both normal and pathological brain processes associated with aging. Studies in animals and humans have shown that during both early childhood and old age the brain is particularly sensitive to stress, probably because it undergoes such important changes during these periods. Furthermore, research now relates exposure to early-life stress with increased reactivity to stress and cognitive deficits in adulthood, indicating that the effects of stress at different periods of life interact. Stress triggers the activation of the hypothalamuspituitary-adrenal (HPA) axis, culminating in the production of glucocorticoids by the adrenals (FIG. ). Receptors for these steroids are expressed throughout the brain; they can act as transcription factors and so regulate gene expression. Thus, glucocorticoids can have potentially long-lasting effects on the functioning of the brain regions that regulate their release. This Review describes the effects of stress during prenatal life, infancy, adolescence, adulthood and old age on the brain, behaviour and cognition, using data from animal (BOX 1) and human studies. Here, we propose a model that integrates the effects of stress across the lifespan, along with future directions for stress research. Animal studies. In animals, exposure to stress early in life has 'programming' effects on the HPA axis and the brain 1 . A single or repeated exposure of a pregnant female to stress 2 or to glucocorticoids 3 increases maternal glucocorticoid secretion. A portion of these glucocorticoids passes through the placenta to reach the fetus, increasing fetal HPA axis activity and modifying brain development . In rats prenatal stress leads to long-term increases in HPA axis activity 5 . Controlling glucocorticoid levels in stressed dams by adrenalectomy and hormone replacement prevents these effects, indicating that elevations in maternal glucocorticoids mediate the prenatal programming of the HPA axis 6 . Glucocorticoids are important for normal brain maturation: they initiate terminal maturation, remodel axons and dendrites and affect cell survival 7 ; both suppressed and elevated glucocorticoid levels impair brain development and functioning. For example, administration of synthetic glucocorticoids to pregnant rats delays the maturation of neurons, myelination, glia and vasculature in the offspring, significantly altering neuronal structure and synapse formation and inhibiting neurogenesis 4 . Furthermore, juvenile and adult rats exposed to prenatal stress have decreased numbers of mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in the hippocampus, possibly because of epigenetic effects on gene transcription 8 . The hippocampus

Hippocampus, 2009

Increased activation of the hypothalamus pituitary adrenal (HPA) axis, marked by increased secretion of cortisol, is a biological marker of psychological stress. It is well established that the hippocampus plays an important role in the regulation of HPA axis activity. The relationship between cortisol (stress-related elevation or exogenous administration) and the hippocampal-related cognitive function is often examined. However, few human studies to date have examined the effect of stress on hippocampal activity and the interactions between stress-induced activation of the HPA axis and hippocampal function during different phases of cognitive function. On the basis of our previous work, we hypothesized that group differences in stress-sensitivity relate to differences in hippocampal-related stress-integration. To test this hypothesis, we conducted a functional MRI study using tasks known to involve the hippocampal formation: novel-picture encoding, psychological stress, and paired-picture recognition. On the basis of their cortisol responses to stress, we divided subjects into stress-responders (increase in cortisol, n 5 9) and nonresponders (decrease in cortisol, n 5 10). Responders showed higher hippocampal deactivation during the stress task and lower recognition scores due to a larger number of misses. Intriguingly, stress-responders showed significant differences in hippocampal activation already prior to stress, with higher levels of hippocampal activity during the picture encoding. Although effects of both cortisol and hippocampal activation on recognition were present in responders, similar effects were absent in the nonresponder group. Our results indicate that hippocampus plays an important role in adaptive behavioral responses. We hypothesize that states of hippocampal activation prior to stress might reflect states of vigilance or anxiety, which might be important for determining interindividual differences in subsequent stress response and cognitive performance. V V C 2009 Wiley-Liss, Inc.

Science, 2009

Brain Rewiring After Stress Chronic stress, mainly through the release of corticosteroids, affects executive behavior through sequential structural modulation of brain networks. Stress-induced deficits in spatial reference, working memory, and behavioral flexibility are associated with synaptic and dendritic reorganization in both the hippocampus and the medial prefrontal cortex. However, the effects of chronic stress on action selection strategies are unclear. Dias-Ferreira et al. (p. 621 ) examined whether chronic stress affects the ability of animals to select the appropriate actions based on the consequences of their choice, and found that rats exposed to chronic unpredictable stress rapidly shift toward using habitual strategies. The shift in behavioral strategies observed in chronically stressed animals corresponded to dramatic and divergent changes in connectivity in the associative and sensorimotor corticostriatal circuits underlying these behaviors.

2007

I. Introduction II. Physiological and Behavioral Factors in Brain and Body Aging Across the Life Span A. Stress, aging, and the hippocampus B. Role of 11-hydroxysteroid dehydrogenase type 1 and other regulators of glucocorticoid availability C. Metabolic hormones affect the hippocampus D. Experiential determinants of brain and body aging E. Animal models of early life experience F. Genetic factors III. Protective and Damaging Effects of Stress Mediators A. Stress, allostasis, and allostatic load B. Protection and damage: the two sides of the response to stressors C. Stress in the natural world D. Being "stressed out": example of sleep deprivation and its consequences IV. The Brain as a Target of Stress and Allostatic Load A. The hippocampus: stress-induced excitability enhancement versus suppression B. The hippocampus: structural remodeling C. Variable glucocorticoid involvement in structural plasticity D. Prefrontal cortex and amygdala E. Interactions between amygdala, prefrontal cortex, and hippocampus F. Sex differences in stress effects V. Translation to Human Brain, Behavior, and Social Organization A. Brain structure and function B. Stress, fatigue, and idiopathic pain disorders C. Stress and cognitive control of food intake D. New insights into positive health and self-esteem as brain-body interactions E. Socioeconomic status and health VI. Management of Chronic Stress and Allostatic Load and Overload A. Brain-centered interventions B. Pharmaceutical agents C. Physical activity D. Social support VII. Conclusions

Neural plasticity, 2007

Stress is a potent modulator of learning and memory processes. Although there have been a few attempts in the literature to explain the diversity of effects (including facilitating, impairing, and lack of effects) described for the impact of stress on memory function according to single classification criterion, they have proved insufficient to explain the whole complexity of effects. Here, we review the literature in the field of stress and memory interactions according to five selected classifying factors (source of stress, stressor duration, stressor intensity, stressor timing with regard to memory phase, and learning type) in an attempt to develop an integrative model to understand how stress affects memory function. Summarizing on those conditions in which there was enough information, we conclude that high stress levels, whether intrinsic (triggered by the cognitive challenge) or extrinsic (induced by conditions completely unrelated to the cognitive task), tend to facilitate Pavlovian conditioning (in a linear-asymptotic manner), while being deleterious for spatial/explicit information processing (which with regard to intrinsic stress levels follows an inverted U-shape effect). Moreover, after reviewing the literature, we conclude that all selected factors are essential to develop an integrative model that defines the outcome of stress effects in memory processes. In parallel, we provide a brief review of the main neurobiological mechanisms proposed to account for the different effects of stress in memory function. Glucocorticoids were found as a common mediating mechanism for both the facilitating and impairing actions of stress in different memory processes and phases. Among the brain regions implicated, the hippocampus, amygdala, and prefrontal cortex were highlighted as critical for the mediation of stress effects.

Acta Neuropathologica, 2014

broad definition of pathology, we here review the "neuropathology of stress" and focus on structural consequences of stress exposure for different regions of the rodent, primate and human brain. we discuss cytoarchitectural, neuropathological and structural plasticity measures as well as more recent neuroimaging techniques that allow direct monitoring of the spatiotemporal effects of stress and the role of different cNS structures in the regulation of the hypothalamic-pituitary-adrenal axis in human brain. we focus on the hypothalamus, hippocampus, amygdala, nucleus accumbens, prefrontal and orbitofrontal cortex, key brain regions that not only modulate emotions and cognition but also the response to stress itself, and discuss disorders like Abstract environmental challenges are part of daily life for any individual. In fact, stress appears to be increasingly present in our modern, and demanding, industrialized society. virtually every aspect of our body and brain can be influenced by stress and although its effects are partly mediated by powerful corticosteroid hormones that target the nervous system, relatively little is known about when, and how, the effects of stress shift from being beneficial and protective to becoming deleterious. Decades of stress research have provided valuable insights into whether stress can directly induce dysfunction and/or pathological alterations, which elements of stress exposure are responsible, and which structural substrates are involved. Using a P. J. lucassen

Stress, 2009

Stressors differ in their physiological and behavioral outcomes. One of the major mechanisms by which stressors affect the brain and behavior is alteration in neuronal plasticity. We investigated in the rat the effects of a single exposure to psychophysical (electrical foot shock) vs. psychological (social defeat) stressors on anxiety-and depression-related behaviors, serum levels of corticosterone and the expression of plasticity-related genes CAM-L1, CREB, GAP-43, and laminin in the prefrontal cortex (PFC), the amygdala and the hippocampus. Rats were examined for 24 h or 1 week after the exposure to stress. Footshocks enhanced anxiety-related behaviors, whereas social defeat induced depression-related behaviors at both time points and less pronounced anxiety 1 week post-exposure. Serum corticosterone concentrations were enhanced 24 h after shocks, but only 1 week after exposure to the social stressor. Moreover, the shock-stressed rats exhibited decreased CAM-L1 protein level in the hippocampus 24 h post-exposure and decreased GAP-43 protein level in the PFC 1 week post-exposure. By contrast, the social stressor enhanced expression of the plasticity-related proteins in the amygdala and the hippocampus, mostly 1 week after the exposure. These results indicate stressor-specific time-dependent changes in different neuronal pathways, and suggest consideration of a cause-specific approach to the treatment of stress-related disorders.

Annals of the New York Academy of Sciences, 1986

The view has repeatedly been expressed that aversive events may increase vulnerability to a wide range of psychological disturbances, including clinical depression. While not dismissing the contribution of cognitive alterations in the provocation of affective disorders, it has been maintained that the neurochemical consequences associated with aversive events are responsible for the depressive symptomatology.'.2 Specifically, it was proposed that when an organism is confronted with a stressor, it will adopt any of a number of behavioral styles in order to escape from the insult or to diminish its impact. Concurrently, a series of neurochemical changes may occur, whose function may be one of either blunting the physical or psychological impact of the stressor or enabling the organism to emit appropriate responses to deal effectively with the stressor. Failure of these adaptive mechanisms may render the organism more vulnerable to behavioral depression. In the present report we document both transient and persistent neurochemical sequelae of stressors and relate these to the behavioral consequences associated with psychological and physical insults. ADAPTIVE NEUROCHEMICAL CHANGES IN RESPONSE TO AVERSIVE STIMULI Although stressful events provoke several neurochemical and hormonal variations, the present report will focus on only two of these, specifically norepinephrine (NE) and dopamine (DA). Omission of other transmitters and hormones does not imply that they are of lesser importance. Indeed, as will be seen later, the very great number of behavioral alterations associated with stressors, and their potential modification by various types of pharmacological manipulations, provide prima facie evidence that transmitters other than the catecholamines are also associated with the behavioral effects of uncontrollable aversive events. asupported by Grants A9845 and A1087 from the Natural Sciences and Engineering Research Council of Canada and Grants MT-6486 and MA-8130 from the Medical Research Council of Canada. 20s 206 ANNALS NEW YORK ACADEMY OF SCIENCES Norepinephrine W Re-exposure 10 Re-exposme to Re-exposure to UncontroUsMe Stress Uffionlrollable Stress Unconlrollable Stress 60 shocks on the first day and 10 shocks on the second day. (From Anisman et al? With permission from Academic Press.