Brain adaptation to stressful stimuli: a new perspective on potential therapeutic approaches based on BDNF and NMDA receptors.
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 cross-tolerance 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.
Marini
Ann M
AM
Department of Neurology and Neuroscience Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA. amarini@usuhs.mil
Popolo
Margherita
M
Pan
Hongna
H
Blondeau
Nicolas
N
Lipsky
Robert H
RH
D000222:Adaptation, Physiological / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology; D003847:Deoxyglucose / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019194:Ischemic Preconditioning / Q000379:methods*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009574:Nitro Compounds / Q000494:pharmacology / Q000627:therapeutic use; D011422:Propionates / Q000494:pharmacology / Q000627:therapeutic use; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects* / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; D016194:Receptors, N-Methyl-D-Aspartate; D003847:Deoxyglucose; C015392:3-nitropropionic acid