期刊
ANTIOXIDANTS & REDOX SIGNALING
卷 28, 期 18, 页码 1724-1745出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2017.7111
关键词
aging; Ca2+ signaling; cognition; NMDA receptor; oxidative stress; redox regulation
资金
- National Institutes of Aging [R01AG037984, R37AG036800, R01AG049711, RO1AG052258]
- Evelyn F. McKnight Brain Research Foundation
Significance: Oxidative stress increases in the brain with aging and neurodegenerative diseases. Previous work emphasized irreversible oxidative damage in relation to cognitive impairment. This research has evolved to consider a continuum of alterations, from redox signaling to oxidative damage, which provides a basis for understanding the onset and progression of cognitive impairment. This review provides an update on research linking redox signaling to altered function of neural circuits involved in information processing and memory. Recent Advances: Starting in middle age, redox signaling triggers changes in nervous system physiology described as senescent physiology. Hippocampal senescent physiology involves decreased cell excitability, altered synaptic plasticity, and decreased synaptic transmission. Recent studies indicate N-methyl-D-aspartate and ryanodine receptors and Ca2+ signaling molecules as molecular substrates of redox-mediated senescent physiology. Critical Issues: We review redox homeostasis mechanisms and consider the chemical character of reactive oxygen and nitrogen species and their role in regulating different transmitter systems. In this regard, senescent physiology may represent the co-opting of pathways normally responsible for feedback regulation of synaptic transmission. Furthermore, differences across transmitter systems may underlie differential vulnerability of brain regions and neuronal circuits to aging and disease. Future Directions: It will be important to identify the intrinsic mechanisms for the shift in oxidative/reductive processes. Intrinsic mechanism will depend on the transmitter system, oxidative stressors, and expression/activity of antioxidant enzymes. In addition, it will be important to identify how intrinsic processes interact with other aging factors, including changes in inflammatory or hormonal signals.
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