Neurochemistry international
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The naturally occurring, non-essential amino acid beta-N-methylamino-L-alanine (BMAA) has been recently found in high concentrations in brain tissues of patients with tauopathies such as the Amyotrophic Lateral Sclerosis-Parkinsonism-Dementia Complex (ALS/PDC) in the South Pacific island of Guam and in a small number of Caucasian, North American patients with sporadic Alzheimer's disease. BMAA is produced by cyanobacteria that are present in all conceivable aquatic and/or terrestrial ecosystems and may be accumulated in living tissues in free and protein-bound forms through the process of biomagnification. ⋯ Glutamate-related excitotoxicity is among the most prominent factors in the etiopathogenesis of human neurodegenerative diseases. Due to the wide geographical distribution of cyanobacteria and the possible implications of BMAA neurotoxic properties in public health more research towards this direction is warranted.
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According to the astrocyte-neurone-lactate shuttle (ANLS) hypothesis, activated neurones use lactate released by astrocytes as their energy substrate. The hypothesis, based largely on in vitro experiments, postulates that lactate is derived from the uptake by astrocytes of synaptically released glutamate. The time course of changes in lactate, derived from in vivo experiments, is incompatible with the ANLS model. ⋯ This rise in lactate occurs too late to provide energy for neuronal activity. Furthermore, there is no evidence that lactate undergoes local oxidative phosphorylation. In conclusion, under physiological conditions, there is no evidence that lactate is a significant source of energy for activated neurones.
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In acute liver failure (ALF) patients that have raised increased intracranial pressure (ICP), mortality remains unacceptably high. There has been an explosion in the knowledge about the pathophysiological basis of raised ICP but treatment modalities are limited. Current therapy is aimed at reducing the circulating ammonia levels and attempts to reduce brain swelling which are only moderately effective. ⋯ The application of moderate hypothermia to treat uncontrolled intracranial hypertension seems promising and its exact place will be decided in a large trial being planned in USA and Europe. Early data from studies in an animal model suggests that albumin dialysis is a promising new tool to treat intracranial hypertension in patients with ALF. The recent advance in our understanding of the pathophysiological basis of intracranial hypertension has provided the platform for the discovery of new treatments.
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The adult hypothalamo-neurohypophysial system (HNS) undergoes activity-dependent morphological plasticity which modifies astrocytic coverage of its oxytocinergic neurons and their synaptic inputs. Thus, during physiological conditions that enhance central and peripheral release of oxytocin (OT), adjacent somata and dendrites of OT neurons become extensively juxtaposed, without intervening astrocytic processes and receive an increased number of synapses. The morphological changes occur within a few hours and are reversible with termination of stimulation. ⋯ Tenascin-C, on the other hand, possesses adhesive and repulsive properties; it is secreted by HNS astrocytes and occurs in extracellular spaces and on cell surfaces after interaction with appropriate ligands. These molecules have been considered permissive factors for morphological plasticity. However, because of their localization and inherent properties, they may also serve to modulate the extracellular environment and in consequence, synaptic and volume transmission in a system in which the extracellular compartment is constantly being modified.
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Mitochondria are central to both apoptotic and necrotic cell death, as well as to normal physiological function. Astrocytes are crucial for neuronal metabolic, antioxidant, and trophic support, as well as normal synaptic function. In the setting of stress, such as during cerebral ischemia, astrocyte dysfunction may compromise the ability of neurons to survive. ⋯ Bcl-2 family proteins are the best studied regulators of cell death, especially apoptosis, and mitochondria are a major site of action for these proteins. Although much data supports the role of Bcl-2 family proteins in the regulation of some of these mitochondrial alterations, this remains an area of active investigation. This mini-review summarizes current knowledge regarding mitochondrial control of cell survival and death in astrocytes and the effects of anti-apoptotic Bcl-2 proteins on astrocyte mitochondrial function.