Physiological and pharmacological characterization of a molluscan neuronal efflux transporter; evidence for age-related transporter impairment.

Plasma membrane efflux transporters play crucial roles in the removal and release of both harmful and beneficial substances from the interior of cells and tissue types in virtually every extant species. They contribute to the clearance of a broad spectrum of exogenous and endogenous toxicants and harmful metabolites, including the reactive lipid aldehyde byproducts of lipid peroxidation that are a hallmark of cellular ageing. Here, we tested whether declining transporter functionality may contribute to functional decline in a snail model of neuronal ageing.

Linking the 'why' and 'how' of ageing: evidence for somatotropic control of long-term memory function in the pond snail .

Organisms live on a budget; hence, they cannot maximize all their activities at the same time. Instead, they must prioritize how they spend limiting resources on the many processes they rely on in their lives. Among others, they are thought to economize on the maintenance and repair processes required for survival in favour of maximizing reproduction, with ageing as a consequence.

Embryonic exposure to model naphthenic acids delays growth and hatching in the pond snail Lymnaea stagnalis.

Naphthenic acids (NAs), a class of structurally diverse carboxylic acids with often complex ring structures and large aliphatic tail groups, are important by-products of many petrochemical processes including the oil sands mining activity of Northern Alberta. While it is evident that NAs have both acute and chronic harmful effects on many organisms, many aspects of their toxicity remain to be clarified. Particularly, while substantive data sets have been collected on NA toxicity in aquatic prokaryote and vertebrate model systems, to date, nothing is known about the toxic effects of these compounds on the embryonic development of aquatic invertebrate taxa, including freshwater mollusks.

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.

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.

Oxidative-stress induced increase in circulating fatty acids does not contribute to phospholipase A2-dependent appetitive long-term memory failure in the pond snail Lymnaea stagnalis.

Background: Reactive oxygen species (ROS) are essential for normal physiological functioning of the brain. However, uncompensated increase in ROS levels may results in oxidative stress. Phospholipase A2 (PLA2) is one of the key players activated by elevated ROS levels resulting in the hydrolysis of various products from the plasmamembrane such as peroxidized fatty acids.

Diminishing glutathione availability and age-associated decline in neuronal excitability.

Oxidative stress is frequently implicated in diminished electrical excitability of aging neurons yet the foundations of this phenomenon are poorly understood. This study explored links between alterations in cellular thiol-redox state and age-associated decline in electrical excitability in identified neurons (right pedal dorsal 1 [RPeD1]) of the gastropod Lymnaea stagnalis. Intracellular thiol redox state was modulated with either dithiothreitol or membrane permeable ethyl ester of the antioxidant glutathione (et-GSH).

Evidence for inflammation-mediated memory dysfunction in gastropods: putative PLA2 and COX inhibitors abolish long-term memory failure induced by systemic immune challenges.

Background: Previous studies associate lipid peroxidation with long-term memory (LTM) failure in a gastropod model (Lymnaea stagnalis) of associative learning and memory. This process involves activation of Phospholipase A2 (PLA2), an enzyme mediating the release of fatty acids such as arachidonic acid that form the precursor for a variety of pro-inflammatory lipid metabolites. This study investigated the effect of biologically realistic challenges of L.

Failure of delayed nonsynaptic neuronal plasticity underlies age-associated long-term associative memory impairment.

Background: Cognitive impairment associated with subtle changes in neuron and neuronal network function rather than widespread neuron death is a feature of the normal aging process in humans and animals. Despite its broad evolutionary conservation, the etiology of this aging process is not well understood. However, recent evidence suggests the existence of a link between oxidative stress in the form of progressive membrane lipid peroxidation, declining neuronal electrical excitability and functional decline of the normal aging brain.

Phospholipase A₂: the key to reversing long-term memory impairment in a gastropod model of aging.

Memory failure associated with changes in neuronal circuit functions rather than cell death is a common feature of normal aging in diverse animal species. The (neuro)biological foundations of this phenomenon are not well understood although oxidative stress, particularly in the guise of lipid peroxidation, is suspected to play a key role. Using an invertebrate model system of age-associated memory impairment that supports direct correlation between behavioral deficits and changes in the underlying neural substrate, we show that inhibition of phospholipase A(2) (PLA(2)) abolishes both long-term memory (LTM) and neural defects observed in senescent subjects and subjects exposed to experimental oxidative stress.

Evidence for age-dependent mating strategies in the simultaneous hermaphrodite snail, Lymnaea stagnalis (L.).

In many mating systems female reproductive capacity is a limiting resource over which males will compete. As a consequence, males and females have usually different fitness optimization strategies which may give rise to sexual conflict. Since simultaneous hermaphrodites have, in theory, the option to mate as male or as female at any time, conflict will occur if partners insist in taking the same role.

RGD-dependent mechanisms in the endoneurial phagocyte response and axonal regeneration in the nervous system of the snail Lymnaea stagnalis.

Activation of phagocytic cells in the injury zone is a crucial step in the regeneration of peripheral axons. Many aspects of the mechanisms underlying the recruitment of active phagocytes remain, however, unclear. Notably, our understanding of the interactions between injury, extracellular matrix (ECM) degradation and phagocyte activation is limited.

Impairment of long-term associative memory in aging snails (Lymnaea stagnalis).

Age-dependent impairment in learning and memory functions occurs in many animal species, including humans. Although cell death contributes to age-related cognitive impairment in pathological forms of aging, learning and memory deficiencies develop with age even without substantial cell death. The molecular and cellular basis of this biological aging process is not well understood but seems to involve a decline in the aging brain's capacity for experience-dependent plasticity.

Epidermal growth factor-dependent enhancement of axonal regeneration in the pond snail Lymnaea stagnalis: role of phagocyte survival.

Peripheral nerve injury triggers complex responses from neuronal as well as from multiple nonneuronal cell types. These responses are coordinated by a wide spectrum of secreted and nonsecreted factors, including growth factors, cytokines, and cell adhesion molecules. These molecules originate from different sources and act both locally at the site of injury as well as centrally at the location of the neuronal cell bodies.

Attenuation of knee joint inflammation by peripherally administered endomorphin-1.

Endomorphin-1 is a selective endogenous ligand for the micro-opioid receptor, and this study investigated the effect of endomorphin-1 on rat knee joint inflammation by examining the ability of the neuropeptide to modulate synovial protein extravasation. Acute joint inflammation was induced by intraarticular injection of 2% kaolin followed by 2% carrageenan and the animals allowed to recover for 3 h. Immunohistochemical examination of these inflamed joints revealed endomorphin-1-like immunoreactive nerves in deep synovium with a proportion of the nerve fibers occurring in close proximity to synovial blood vessels.

Electroporation of proviral RCAS DNA alters gene expression in the embryonic chick hindbrain.

Gene transfer by means of electroporation is an effective method for delivering DNA into cells. Expression vectors encoding green fluorescent protein (GFP) are routinely used as a control for this technique and are also regularly used to indirectly or directly monitor the expression of introduced transgenes. However, recent studies suggest that GFP may have nonspecific and/or cytotoxic side effects.

Rapid neuromodulatory actions of integrin ligands.

Extracellular matrix (ECM) proteins and their receptors, the integrins, actively participate in the control of many fundamental cellular functions in the developing nervous system, including the regulation of cell migration, differentiation, and survival and the control of neurite outgrowth. ECM-integrin interactions in the mature nervous system are commonly considered to be more static in nature and of little importance in the regulation of neuronal function. In contrast, we demonstrate that integrins and their ligands are capable of rapid neuromodulatory actions.