Neuronal Responses to Physiological Stress

Abstract

Physiological stress can be defined as any external or internal condition that challenges the homeostasis of a cell or an organism. It can be divided into three different aspects: environmental stress, intrinsic developmental stress, and aging. Throughout life all living organisms are challenged by changes in the environment. Fluctuations in oxygen levels, temperature, and redox state for example, trigger molecular events that enable an organism to adapt, survive, and reproduce. In addition to external stressors, organisms experience stress associated with morphogenesis and changes in inner chemistry during normal development. For example, conditions such as intrinsic hypoxia and oxidative stress, due to an increase in tissue mass, have to be confronted by developing embryos in order to complete their development. Finally, organisms face the challenge of stochastic accumulation of molecular damage during aging that results in decline and eventual death. Studies have shown that the nervous system plays a pivotal role in responding to stress. Neurons not only receive and process information from the environment but also actively respond to various stresses to promote survival. These responses include changes in the expression of molecules such as transcription factors and microRNAs that regulate stress resistance and adaptation. Moreover, both intrinsic and extrinsic stresses have a tremendous impact on neuronal development and maintenance with implications in many diseases. Here, we review the responses of neurons to various physiological stressors at the molecular and cellular level.

Gene expression during testis development in Duroc boars

“…These have a protective role during increased steroidogenesis. However, a potent redox/detox battery is also essential for the vitality and renewal of neurons during development (Kagias et al, 2012). Little has been reported on neuronal development in the boar testis, but there are studies in humans and rats (Gerendai et al, 2005).…”

Shining a light on early stress responses and late-onset disease vulnerability

“…Previous work has defined the effects of a more limited set of perturbations or stressor states on stress-responsive regions of the brain and on defining stress-responsive regulatory processes that mediate signal efficacy and effector functions (8,9). These studies have also emphasized that stress-responsive transcription factors participate in a dynamic array of transcriptional processes that mediate a wide variety of normal and pathological biological functions (9, 10).…”

“…However, until now the potential to contextualize these biological properties arrayed in time and space and in relation to ongoing stress-mediated impairments and compensatory mechanisms underpinning normal physiological processes, disease vulnerabilities, and comorbidities have remained elusive. Stress responses represent evolutionarily conserved mechanisms involved in normal physiological processes, and in response to disease states, genetic predispositions, and transgenerational influences (9). Stress-responsive transcription factors, microRNAs, and associated signaling molecules/pathways mediate these multipronged adaptations (9) (Fig.…”

“…Stress responses represent evolutionarily conserved mechanisms involved in normal physiological processes, and in response to disease states, genetic predispositions, and transgenerational influences (9). Stress-responsive transcription factors, microRNAs, and associated signaling molecules/pathways mediate these multipronged adaptations (9) (Fig. 1).…”

“…Through interrogation of these processes, we are beginning to gain insight into the coordination of gene expression among target cells, tissues/organs, and organismal responses to developmental and age-related processes in health and disease. HSF1 and other stress-responsive factors are modulated by DNA binding and protein-protein interactions, posttranslational modifications, protein degradation pathways, epigenetic mechanisms, posttranscriptional processing, intracellular localization, cell cycle regulation and metabolic states of effector cells, autoregulation and feed-forward signaling, cross-tolerance and cross-adaptation, as well as preconditioning (9,10). Physiological stress responses during development and aging may be coordinately linked through neuronal/neural network response pathways by specific proneural and other (FOXO) transcription factors that preserve stem cell quiescence and the integrity of stem/progenitor pools, prevent loss of neuronal subtype identity/ functions, maintain neuronal homeostasis and survival, and orchestrate cell type-specific and interorgan communications that promote adaptations associated with longevity (11).…”