Rapid removal of glutamate from the extracellular space is required for the survival and normal function of neurons. Although glutamate transporters are expressed by all CNS cell types, astrocytes are the cell type primarily responsible for glutamate uptake. Astrocyte glutamate uptake also plays a role in regulating the activity of glutamatergic synapses. Lastly, release of glutamate from astrocytes, via transporter reversal and other routes, can contribute to glutamate receptor activation. This review examines the mechanisms of astrocyte glutamate uptake and release, with particular focus on high-affinity Na+-dependent transporters. Transporter regulation, energetics, and physiological roles are discussed. GLIA 32:1–14, 2000. Published 2000 Wiley-Liss, Inc.

Astrocyte glutamate transport: Review of properties, regulation, and physiological functions †

The long-term behavioural consequences of prenatal stress.

The balance between oxidation and antioxidation is believed to be critical in maintaining healthy biological systems. Under physiological conditions, the human antioxidative defense system including e.g., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) and others, allows the elimination of excess reactive oxygen species (ROS) including, among others superoxide anions (O2(·-)), hydroxyl radicals (OH·), alkoxyl radicals (RO·) and peroxyradicals (ROO·). However, our endogenous antioxidant defense systems are incomplete without exogenous originating reducing compounds such as vitamin C, vitamin E, carotenoids and polyphenols, playing an essential role in many antioxidant mechanisms in living organisms. Therefore, there is continuous demand for exogenous antioxidants in order to prevent oxidative stress, representing a disequilibrium redox state in favor of oxidation. However, high doses of isolated compounds may be toxic, owing to prooxidative effects at high concentrations or their potential to react with beneficial concentrations of ROS normally present at physiological conditions that are required for optimal cellular functioning. This review aims to examine the double-edged effects of dietary originating antioxidants with a focus on the most abundant compounds, especially polyphenols, vitamin C, vitamin E and carotenoids. Different approaches to enrich our body with exogenous antioxidants such as via synthetic antioxidants, diets rich in fruits and vegetables and taking supplements will be reviewed and experimental and epidemiological evidences discussed, highlighting that antioxidants at physiological doses are generally safe, exhibiting interesting health beneficial effects.

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Exogenous antioxidants--Double-edged swords in cellular redox state: Health beneficial effects at physiologic doses versus deleterious effects at high doses.

Oxidative stress has been implicated in the pathogenesis of diverse disease states, and may be a common pathogenic mechanism underlying many major psychiatric disorders, as the brain has comparatively greater vulnerability to oxidative damage This review aims to examine the current evidence for the role of oxidative stress in psychiatric disorders, and its academic and clinical implications A literature search was conducted using the Medline, Pubmed, PsycINFO, CINAHL PLUS, BIOSIS Previews, and Cochrane databases, with a time-frame extending to September 2007 The broadest data for oxidative stress mechanisms have been derived from studies conducted in schizophrenia, where evidence is available from different areas of oxidative research, including oxidative marker assays, psychopharmacology studies, and clinical trials of antioxidants For bipolar disorder and depression, a solid foundation for oxidative stress hypotheses has been provided by biochemical, genetic, pharmacological, preclinical therapeutic studies and one clinical trial Oxidative pathophysiology in anxiety disorders is strongly supported by animal models, and also by human biochemical data Pilot studies have suggested efficacy of N-acetylcysteine in cocaine dependence, while early evidence is accumulating for oxidative mechanisms in autism and attention deficit hyperactivity disorder In conclusion, multi-dimensional data support the role of oxidative stress in diverse psychiatric disorders These data not only suggest that oxidative mechanisms may form unifying common pathogenic pathways in psychiatric disorders, but also introduce new targets for the development of therapeutic interventions

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Oxidative stress in psychiatric disorders : evidence base and therapeutic implications

Modern research has provided new insights into the biological mechanisms of noise-induced hearing loss, and with these new insights comes hope for possible prevention or treatment. Underlying the classic set of cochlear pathologies that occur as a result of noise exposure are increased levels of reactive oxygen species (ROS) that play a significant role in noise-induced hair cell death. Both necrotic and apoptotic cell death have been identified in the cochlea. Included in the current review is a brief review of ROS, along with a description of sources of cochlear ROS generation and how ROS can damage cochlear tissue. The pathways of necrotic and apoptotic cell death are also reviewed. Interventions are discussed that target the prevention of noise-induced hair cell death: the use of antioxidants to scavenge and eliminate the damaging ROS, pharmacological interventions to limit the damage resulting from ROS, and new techniques aimed at interrupting the apoptotic biochemical cascade that results in the death of irreplaceable hair cells.

The role of oxidative stress in noise-induced hearing loss.

Anxiolytic properties of green tea polyphenol (-)-epigallocatechin gallate (EGCG).

Sex differences in learning deficits induced by prenatal stress in juvenile rats.

Glutamate is considered to be one of the most common neurotransmitters in the fast excitatory synapses in the central nervous system. On the other hand, its excitotoxic properties are increasingly cited to explain some of the brain damage linked with hypoxia and ischaemia: i.e., those that occur frequently in ageing. An excess release of glutamate could, either directly or indirectly, activate receptors on the postsynaptic neuron, causing ion influxes accompanied by a massive entry of water, which would lead to an acute swelling of dendrites. In addition, calcium influx deregulates calcium homeostasis, which could lead to cell death. In the cochlea, glutamate is now considered to be one of the best candidates to mediate neurotransmission between inner hair cells (IHCs) and the auditory nerve dendrites. Among the variety of anatomical and physiological findings supporting the glutamate hypothesis, is the striking similarity of acute damage in the organ of Corti caused by exposure to a glutamate analogue (kainic acid), or by hypoxia, or even by an intense loud noise. In all cases an immediate swelling is observed, specifically affecting the radial afferents below the IHCs. The best explanation for this swelling is related to glutamate (or glutamate analogue) excitotoxicity. Thus, some of the cochlear damage that occur with ageing, especially the loss of the radial afferent fibres and type I ganglion cells, might well be attributed to glutamate excitotoxicity linked to vascular atrophy. The present paper discusses this hypothesis.

Glutamate Neurotoxicity in the Cochlea: A Possible Consequence of Ischaemic or Anoxic Conditions Occurring in Ageing

The extracellular glutamate concentration is kept low by glutamate transporters in the plasma membranes. Here we have studied the expression of the glutamate transporters GLAST, GLT and EAAC during the in vitro development of embryonic hippocampal neurons grown in a defined (serum free) medium. Immunochemistry studies showed that both the GLAST and GLT proteins are expressed in a subpopulation of neurons at the early, but not at the later stages of the cultures. Glial cells expressing the GLAST and GLT proteins were found at all stages. EAAC was only detected in neurons. This is one of the first evidence of a neuronal ability to express GLAST. J. Neurosci. Res. 59:587‐593, 2000. © 2000 Wiley-Liss, Inc.

Transient expression of the glial glutamate transporters GLAST and GLT in hippocampal neurons in primary culture.

Low frequency-induced short-term synaptic plasticity was investigated in hippocampal slices with 60-electrode recording array. Remarkably, the application of low-frequency stimulation (1 Hz) for a short duration (3-5 min) resulted in the induction of a slow-onset long-term potentiation (LTP) in the immediate vicinity of the stimulated electrode. This phenomenon was observed exclusively in the CA1 subfield, neither in the CA3 area nor in the dentate gyrus. The induction of this slow-onset LTP required neither N-methyl-D-aspartate (NMDA) nor non-NMDA ionotropic receptor activation but was strongly dependent on metabotropic glutamate mGlu(5) receptor stimulation and [Ca(2+)]i increase. In addition, this form of synaptic plasticity was associated with an increase in cAMP concentration and required protein kinase A activation. Paired-pulse facilitation ratio and presynaptic fiber volley amplitude were unaffected when this LTP was triggered, suggesting the involvement of postsynaptic modifications. Although mitogen activated protein kinase pathway was stimulated after the application of low frequency, the induction and maintenance of this slow-onset LTP were not dependent on the activation of this intracellular pathway. The direct activation of adenylyl cyclase with forskolin also induced a synaptic enhancement displaying similar features. This new form of LTP could represent the mnesic engram of mild and repetitive stimulation involved in latent learning.

Low-frequency stimulation induces a new form of LTP, metabotropic glutamate (mGlu5) receptor- and PKA-dependent, in the CA1 area of the rat hippocampus.

Max Récasens

Papers

Anxiolytic properties of green tea polyphenol (-)-epigallocatechin gallate (EGCG).

Sex differences in learning deficits induced by prenatal stress in juvenile rats.

Glutamate Neurotoxicity in the Cochlea: A Possible Consequence of Ischaemic or Anoxic Conditions Occurring in Ageing

Transient expression of the glial glutamate transporters GLAST and GLT in hippocampal neurons in primary culture.

Low-frequency stimulation induces a new form of LTP, metabotropic glutamate (mGlu5) receptor- and PKA-dependent, in the CA1 area of the rat hippocampus.