To study the operational behaviour of λ-terms, we will use the denotational (mathematical) approach. A denotational semantics for a language is based on the choice of a space of semantics values, or denotations, where terms are to be interpreted. Choosing a space with nice mathematical properties can help in proving the semantic properties of terms, since to this aim standard mathematical techniques can be used.

λ Δ -Models

The (n-3) fatty acids are essential dietary nutrients, and one of their important roles is providing docosahexaenoic acid [22:6(n-3)] (DHA) for growth and function of nervous tissue. Reduced DHA is associated with impairments in cognitive and behavioral performance, effects which are particularly important during brain development. Recent studies suggest that DHA functions in neurogenesis, neurotransmission, and protection against oxidative stress. These functions relate to the roles of DHA within the hydrophobic core of neural membranes and effects of unesterified DHA. Reviewed here are some of the recent studies that have begun to elucidate the role of DHA in brain development and function. A better understanding of development and age-specific changes in DHA transfer and function in the developing brain may provide important insight into the role of DHA in developmental disorders in infants and children, as well as at other stages of the lifespan.

Dietary (n-3) Fatty Acids and Brain Development

Stroke is one of the leading causes of mortality and morbidity, with astronomical financial repercussions on health systems worldwide. Ischaemic stroke accounts for approximately 80-85% of all cases and is characterised by the disruption of cerebral blood flow and lack of oxygen to the affected area. Oxidative stress culminates due to an imbalance between pro-oxidants and antioxidants and consequent excessive production of reactive oxygen species. Reactive oxygen species are biphasic, playing a role in normal physiological processes and are also implicated in a number of disease processes, whereby they mediate damage to cell structures, including lipids, membranes, proteins, and DNA. The cerebral vasculature is a major target of oxidative stress playing a critical role in the pathogenesis of ischaemic brain injury following a cerebrovascular attack. Superoxide, the primary reactive oxygen species, and its derivatives have been shown to cause vasodilatation via the opening of potassium channels and altered vascular reactivity, breakdown of the blood-brain barrier and focal destructive lesions in animal models of ischaemic stroke. However, reactive oxygen species are involved in normal physiological processes including cell signalling, induction of mitogenesis, and immune defence. Primarily, this review will focus on the cellular and vascular aspects of reactive oxygen and nitrogen species generation and their role in the pathogenesis of ischaemia-reperfusion phenomena. Secondly, the proposed mechanisms of oxidative stress-related neuronal death will be reflected upon and in summation specific targeted neuroprotective therapies targetting oxidative stress and their role in the pathogenesis of stroke will be discussed.

Oxidative stress and its role in the pathogenesis of ischaemic stroke.

The chemistry and biological activities of N-acetylcysteine

Oxidative stress in neurodegenerative diseases.

Lipid metabolism in vertebrate retinal rod outer segments.

Iron (Fe) is an essential element for many metabolic processes, serving as a cofactor for heme and nonheme proteins Cellular iron deficiency arrests cell growth and leads to cell death; however, like most transition metals, an excess of intracellular iron is toxic The ability of Fe to accept and donate electrons can lead to the formation of reactive nitrogen and oxygen species, and oxidative damage to tissue components; contributing to disease and, perhaps, aging itself It has also been suggested that iron-induced oxidative stress can play a key role in the pathogenesis of several neurodegenerative diseases Iron progressively accumulates in the brain both during normal aging and neurodegenerative processes However, iron accumulation occurs without the concomitant increase in tissue ferritin, which could increase the risk of oxidative stress Moreover, high iron concentrations in the brain have been consistently observed in Alzheimer's disease (AD) and Parkinson's disease (PD) In this regard, metalloneurobiology has become extremely important in understanding the role of iron in the onset and progression of neurodegenerative diseases Neurons have developed several protective mechanisms against oxidative stress, among them the activation of cellular signaling pathways The final response will depend on the identity, intensity, and persistence of the oxidative insult The characterization of the mechanisms involved in high iron induced in neuronal dysfunction and death is central to understanding the pathology of a number of neurodegenerative disorders

Iron in neuronal function and dysfunction

In this review, changes in brain lipid composition and metabolism due to aging are outlined. The most striking changes in cerebral cortex and cerebellum lipid composition involve an increase in acidic phospholipid synthesis. The most important changes with respect to fatty acyl composition involve a decreased content in polyunsaturated fatty acids (20:4n-6, 22:4n-6, 22:6n-3) and an increased content in monounsaturated fatty acids (18:1n-9 and 20:1n-9), mainly in ethanolamine and serineglycerophospholipids. Changes in the activity of the enzymes modifying the phospholipid headgroup occur during aging. Serine incorporation into phosphatidylserine through base-exchange reactions and phosphatidylcholine synthesis through phosphatidylethanolamine methylation increases in the aged brain. Phosphatidate phosphohydrolase and phospholipase D activities are also altered in the aged brain thus producing changes in the lipid second messengers diacylglycerol and phosphatidic acid.

Age-associated changes in central nervous system glycerolipid composition and metabolism.

The accumulation of transition metals (e.g., copper, zinc, and iron) and the dysregulation of their metabolism are a hallmark in the pathogenesis of several neurodegenerative diseases. This paper will be focused on the mechanism of neurotoxicity mediated by iron. This metal progressively accumulates in the brain both during normal aging and neurodegenerative processes. High iron concentrations in the brain have been consistently observed in Alzheimer's (AD) and Parkinson's (PD) diseases. In this connection, metalloneurobiology has become extremely important in establishing the role of iron in the onset and progression of neurodegenerative diseases. Neurons have developed several protective mechanisms against oxidative stress, among them, the activation of cellular signaling pathways. The final response will depend on the identity, intensity, and persistence of the oxidative insult. The characterization of the mechanisms mediating the effects of iron-induced increase in neuronal dysfunction and death is central to understanding the pathology of a number of neurodegenerative disorders.

/pdf/iron-and-mechanisms-of-neurotoxicity-399na513i9.pdf

Gabriela Alejandra Salvador

Papers

Lipid metabolism in vertebrate retinal rod outer segments.

Iron in neuronal function and dysfunction

Age-associated changes in central nervous system glycerolipid composition and metabolism.

Iron and Mechanisms of Neurotoxicity

Enhanced Phosphatidylinositol 3-kinase (PI3K)/Akt Signaling Has Pleiotropic Targets in Hippocampal Neurons Exposed to Iron-Induced Oxidative Stress