Abstract
The aging brain undergoes a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (per)oxidation of membrane lipids and activation of phospholipase A2 (PLA2) enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the biology of cognitive aging we portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain.
Highlights
Most organisms age, humans and the vast majority of other complex animals included
We explore the idea that processes triggered by oxidative stress ensuing at the level of phospholipid bilayer membranes of cells and organelles play a central role in age-associated deterioration of the healthy aging nervous system
We examine howoxidation of methylene-interrupted polyunsaturated fatty acids1 (PUFAs) and subsequent activation of members of the phospholipase A2 (PLA2) family of fatty acylases may play a central role in declining excitability of aging neurons and age-associated memory impairment (AMI; see Figure 1 for conceptual framework; see Figure 2 for mechanisms and potential implications of PUFA peroxidation)
Summary
Humans and the vast majority of other complex animals included. That is, the life functions required for their survival and reproduction weaken as they grow older due to natural processes that are still only partially understood and involve a complex combination of chemical, genetic, metabolic, molecular, physiological, ecological, and evolutionary features (see for instance Kirkwood and Austad, 2000; Ljubuncic and Reznick, 2009; Masoro and Austad, 2011).Aging generally affects all aspects of an organism’s biology including, in the case of humans and complex multicellular animals, the nervous system’s ability to execute its control processes and support learning and memory functions. The list of physiological and biochemical symptoms of neuronal aging is extensive and includes evidence for oxidative stress, impaired energy and redox metabolism, Ca2+ signaling perturbation, accumulating damage to proteins, lipids, nucleic acids and organelles, declining dendritic complexity, alterations in synaptic density, distribution and function, changes in gene regulation, and molecular processes underlying remodeling of synapses (Barnes, 1994; Burke and Barnes, 2006; Mattson and Magnus, 2006; Esiri, 2007; Shankar, 2010; Toescu and Vreugdenhil, 2010; Yeoman et al, 2012).
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