Phospholipase A2 – nexus of aging, oxidative stress, neuronal excitability, and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment

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.

Translationally Controlled Tumor Protein Stimulates Dopamine Release from PC12 Cells via Ca2+-Independent Phospholipase A2 Pathways

“…A direct relationship was proposed between pardaxin-induced dopamine release and the arachidonic acid cascades. Arachidonic acid, a major fatty acid produced by Ca 2+ -dependent or Ca 2+ -independent activation of PLA 2 , serves as a precursor of eicosanoids that mediate diverse physiological and pathophysiological processes in brain and other tissues [19,20]. …”

Lifelong neurogenesis in the cerebral ganglion of the Chinese mud snail,Cipangopaludina chinensis

“…Research on Giant neuron snails, L. stagnalis and Aplysia sp. have documented changes in membrane excitability with age of critical giant neurons and the role of antioxidants in preserving the health of these critical cells (Hermann et al., ; Moroz & Kohn, ). Normal afferent and efferent innervation of new body tissue during adult growth has received very little attention in either vertebrates or invertebrates; probably because it is considered to be simply a continuation of the processes that occur rapidly during early development.…”

Linking the why and how of aging; evidence for somatotropic control of long-term memory function in the pond snail Lymnaea stagnalis

“…Animals were fed ad libitum with a standard diet consisting of Romaine lettuce and Aquamax-carniverous Grower 600 trout pellets (Purina Mills, St Louis, MO, USA). For the present study, fully sexually mature snails (age 7-9 months; shell length 2.5-3.0 cm) were taken at random from an age-synchronized population displaying survival characteristics of healthy ageing populations (see Hermann et al, 2014 for further details on population survival assessment).…”