Abstract
A variety of sublethal or stressful stimuli induce a phenomenon in the brain known as tolerance, an adaptive response that protects the brain against the same stress, or against a different stress (cross-tolerance). Understanding the molecular mechanisms of brain preconditioning holds promise in developing innovative therapies to prevent and treat neurodegenerative disorders, particularly ischemic stroke. Many of the detailed steps involved in tolerance and crosstolerance are unknown. It is also likely that different stressors differentially regulate sets of genes, transcription factors, and signal transduction pathways that depend upon the molecules that are released in response to the stressor, activation of particular receptors, and the surrounding milieu. The focus of this review is to highlight a few examples of stimuli that induce tolerance: 1) cortical spreading depression; 2) 3-nitropropionic acid; and 3) 2-deoxy-D-glucose. We will summarize by discussing one pathway where intracellular mediators may converge to upregulate intrinsic neuronal survival pathways to promote survival by resisting damage. This mechanism, activation of N-methyl-D-aspartate receptors and its integral relationship with brain-derived neurotrophic factor, may be a critical and general mechanism developed in brain to respond to stressful stimuli.
Keywords: Stress, stroke, brain preconditioning, brain tolerance, NMDA receptors, BDNF, TrkB receptors, NF-B
CNS & Neurological Disorders - Drug Targets
Title: Brain Adaptation to Stressful Stimuli: A New Perspective on Potential Therapeutic Approaches Based on BDNF and NMDA Receptors
Volume: 7 Issue: 4
Author(s): Ann M. Marini, Margherita Popolo, Hongna Pan, Nicolas Blondeau and Robert H. Lipsky
Affiliation:
Keywords: Stress, stroke, brain preconditioning, brain tolerance, NMDA receptors, BDNF, TrkB receptors, NF-B
Abstract: A variety of sublethal or stressful stimuli induce a phenomenon in the brain known as tolerance, an adaptive response that protects the brain against the same stress, or against a different stress (cross-tolerance). Understanding the molecular mechanisms of brain preconditioning holds promise in developing innovative therapies to prevent and treat neurodegenerative disorders, particularly ischemic stroke. Many of the detailed steps involved in tolerance and crosstolerance are unknown. It is also likely that different stressors differentially regulate sets of genes, transcription factors, and signal transduction pathways that depend upon the molecules that are released in response to the stressor, activation of particular receptors, and the surrounding milieu. The focus of this review is to highlight a few examples of stimuli that induce tolerance: 1) cortical spreading depression; 2) 3-nitropropionic acid; and 3) 2-deoxy-D-glucose. We will summarize by discussing one pathway where intracellular mediators may converge to upregulate intrinsic neuronal survival pathways to promote survival by resisting damage. This mechanism, activation of N-methyl-D-aspartate receptors and its integral relationship with brain-derived neurotrophic factor, may be a critical and general mechanism developed in brain to respond to stressful stimuli.
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Cite this article as:
Marini M. Ann, Popolo Margherita, Pan Hongna, Blondeau Nicolas and Lipsky H. Robert, Brain Adaptation to Stressful Stimuli: A New Perspective on Potential Therapeutic Approaches Based on BDNF and NMDA Receptors, CNS & Neurological Disorders - Drug Targets 2008; 7 (4) . https://dx.doi.org/10.2174/187152708786441849
DOI https://dx.doi.org/10.2174/187152708786441849 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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