Long-term potentiation of synaptic transmission in the hippocampus is the primary experimental model for investigating the synaptic basis of learning and memory in vertebrates. The best understood form of long-term potentiation is induced by the activation of the N-methyl-D-aspartate receptor complex. This subtype of glutamate receptor endows long-term potentiation with Hebbian characteristics, and allows electrical events at the postsynaptic membrane to be transduced into chemical signals which, in turn, are thought to activate both pre- and postsynaptic mechanisms to generate a persistent increase in synaptic strength.

A synaptic model of memory: long-term potentiation in the hippocampus

The biochemistry and medical significance of the flavonoids.

Excitotoxicity refers to the ability of glutamate or related excitatory amino acids to mediate the death of central neurons under certain conditions, for example, after intense exposure. Such excitotoxic neuronal death may contribute to the pathogenesis of brain or spinal cord injury associated with several human disease states. Excitotoxicity has substantial cellular specificity and, in most cases, is mediated by glutamate receptors. On average, NMDA receptors activation may be able to trigger lethal injury more rapidly than AMPA or kainate receptor activation, perhaps reflecting a greater ability to induce calcium influx and subsequent cellular calcium overload. It is possible that excitotoxic death may share some mechanisms with other forms of neuronal death.

Excitotoxic cell death

The pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) is unknown, but defects in synaptosomal high-affinity glutamate transport have been observed. In experimental models, chronic loss of glutamate transport can produce a loss of motor neurons and, therefore, could contribute to the disease. With the recent cloning of three glutamate transporters, i.e., EAAC1, GLT-1, and GLAST, it has become possible to determine if the loss of glutamate transport in ALS is subtype specific. We developed C-terminal, antioligopeptide antibodies that were specific for each glutamate transporter. EAAC1 is selective for neurons, while GLT-1 and GLAST are selective for astroglia. Tissue from various brain regions of ALS patients and controls were examined by immunoblot or immunocytochemical methods for each transporter subtype. All tissue was matched for age and postmortem delay. GLT-1 immunoreactive protein was severely decreased in ALS, both in motor cortex (71% decrease compared with control) and in spinal cord. In approximately a quarter of the ALS motor cortex specimens, the loss of GLT-1 protein (90% decrease from control) was dramatic. By contrast, there was only a modest loss (20% decrease from control) of immunoreactive protein EAAC1 in ALS motor cortex, and there was no appreciable change in GLAST. The minor loss of EAAC1 could be secondary to loss of cortical motor neurons. As a comparison, glial fibrillary acidic protein, which is selectively localized to astroglia, was not changed in ALS motor cortex. Because there is no loss of astroglia in ALS, the dramatic abnormalities in GLT-1 could reflect a primary defect in GLT-1 protein, a secondary loss due to down regulation, or other toxic processes.

Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis.

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 †

Activation of NMDA (N-methyl-D-aspartate) receptors by neurotransmitter glutamate stimulates phospholipase A2 to release arachidonic acid. This second messenger facilitates long-term potentiation of glutamatergic synapses in the hippocampus, possibly by blocking glutamate uptake. We have studied the effect of arachidonic acid on glutamate uptake into glial cells using the whole-cell patch-clamp technique to monitor the uptake electrically. Micromolar levels of arachidonic acid inhibit glutamate uptake, mainly by reducing the maximum uptake rate with only small effects on the affinity for external glutamate and sodium. On removal of arachidonic acid a rapid (5 minutes) phase of partial recovery is followed by a maintained suppression of uptake lasting at least 20 minutes. Surprisingly, the action of arachidonic acid is unaffected by cyclo-oxygenase or lipoxygenase inhibitors suggesting that it inhibits uptake directly, possibly by increasing membrane fluidity. As blockade of phospholipase A2 prevents the induction of long-term potentiation (LTP), inhibition of glutamate uptake by arachidonic acid may contribute to the increase of synaptic gain that occurs in LTP. During anoxia, release of arachidonic acid could severely compromise glutamate uptake and thus contribute to neuronal death.

Arachidonic acid induces a prolonged inhibition of glutamate uptake into glial cells

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Nick Ingledew

Author Tools

Chat about Author

Papers

Arachidonic acid induces a prolonged inhibition of glutamate uptake into glial cells