Neuropathology of stress

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 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 depression, post-traumatic stress disorder, Cushing syndrome and dementia.

Differential and Converging Molecular Mechanisms of Antidepressants’ Action in the Hippocampal Dentate Gyrus

“…To this end, we here sought to identify common and divergent molecular targets and pathways of four distinct classes of ADs, represented by fluoxetine, imipramine, tianeptine, and agomelatine. Our genome-wide analysis focused on the hippocampal DG-one of the most studied neural targets of stress and ADs (Lucassen et al, 2014;Wainwright and Galea, 2013)-from animals displaying behavioral and endocrine impairments akin to depression. These behavioral anomalies were reversed after 2 weeks of treatment with fluoxetine, imipramine, and tianeptine; agomelatine resulted in only partial behavioral recovery although it re-synchronized the diurnal pattern of corticosterone secretion.…”

“…Although the pathophysiology of depression is still incompletely understood, dysregulation of monoaminergic systems, neuroplasticity, and immunological responses (Villanueva, 2013;Willner et al, 2013) are considered to contribute to the disease. In addition, alterations in dendritic plasticity and cytogenesis in the hippocampal dentate gyrus (DG) are observed in the brains of animal models of depression and depressed patients (Lucassen et al, 2014;Pittenger and Duman, 2008). Importantly, these changes have been implicated in the onset of depressivelike symptoms and in the actions of antidepressants (ADs) in animal models of depression (Bessa et al, 2009a;Mateus-Pinheiro et al, 2013a, b;Surget et al, 2011).…”

“…Exposure to uCMS results in animals with behavioral deficits and biometric and neuroplastic changes that match many of those found in patients with major depression (Bessa et al, 2013(Bessa et al, , 2009bHill et al, 2012;Lucassen et al, 2014). Following induction of disease-like symptoms, animals were treated with either fluoxetine, imipramine, tianeptine, or agomelatine, and transcriptome analysis was subsequently performed on their DGs.…”

Pharmacotherapeutic Effect of Stress Protectors in the Age Aspect

“…Тіоцетам -комбінований препарат, який складається з тіотриазоліну та пірацетаму, відноситься до групи цереброактивних засо-бів, що мають ноотропні, протиішемічні, ан-тиоксидантні та мембраностабілізуючі влас-тивості [16,21,27,28]. Ноотропні ефекти тіо-цетаму у вигляді усунення психогенних нас-лідків стресу та покращення інтегративної й когнітивної діяльності мозку поєднуються з підвищенням активності метаболічного шун-та гамма-аміномасляної кислоти (ГАМК-шунта), модуляцією інтенсивності функціо-нування системи NO і конкуренцією з SH-групами цистеїн-залежних ділянок клітинних білків та нейропептидів.…”

Antidepressant-like activity of red wine phenolic extracts in repeated corticosterone-induced depression mice via BDNF/TrkB/CREB signaling pathway

“…In this classic neuroendocrine circuit, limbic and hypothalamic brain structures coordinate emotional, cognitive, neuroendocrine and autonomic inputs, which together determine the magnitude and specificity of an individual's behavioral, neural and hormonal responses to stress. This response is mediated by glucocorticoid hormones (corticosterone in rodents and cortisol in humans) (Lucassen et al, 2014). Increased level of corticosterone has mostly been ascribed to impaired feedback regulation of the HPA axis, possibly caused by altered function of the glucocorticoid receptor and induced depressive disorder (Lee, Sur, Shim, Lee, & Hahm, 2015).…”