Reduced plasma membrane surface expression of GLAST mediates decreased glutamate regulation in the aged striatum

Justin Nickell, Michael Francis Salvatore, Francois Pomerleau, Subbu Apparsundaram, Greg A. Gerhardt

Research output: Contribution to journalArticleResearchpeer-review

34 Citations (Scopus)

Abstract

Extracellular l-glutamate poses a severe excitotoxic threat to neurons and glia when unregulated, therefore low synaptic levels of this neurotransmitter must be maintained via a rapid and robust transport system. A recent study from our laboratory showed a reduced glutamate uptake rate in the striatum of the aged Fischer 344 (F344) rat, yet the mechanism underlying this phenomenon is unknown. The current study utilized in vivo electrochemical recordings, immunoblotting and biotinylation in young (6 months), late-middle aged (18 months) and aged (24 months) F344 rats to elucidate the potential role that glutamate transporters (GLT-1, GLAST, and EAAC1) may play in this mechanism. Here we show that the time necessary to clear glutamate from the late-middle aged and aged striatum is significantly prolonged in comparison to the young striatum. In addition, an analysis of various sub-regions of the striatum revealed a marked dorsoventral gradient in terms of glutamate clearance times in the aged striatum, a phenomenon which was not present in the striatum of the animals of the remaining age groups. We also found that the decreased glutamate clearance time observed in the late-middle aged and aged rats is not due to a decrease in the production of total transporter protein among these three transporters. Rather, a significant reduction in the amount of GLAST expressed on the plasma membrane surface in the aged animals (∼55% when compared to young rats) may contribute to this phenomenon. These age-related alterations in extracellular l-glutamate regulation may be key contributors to the increased susceptibility of the aged brain to excitotoxic insults such as stroke and hypoxia.

Original languageEnglish
Pages (from-to)1737-1748
Number of pages12
JournalNeurobiology of Aging
Volume28
Issue number11
DOIs
StatePublished - 1 Nov 2007

Fingerprint

Glutamic Acid
Cell Membrane
Inbred F344 Rats
Biotinylation
Amino Acid Transport System X-AG
Immunoblotting
Neuroglia
Neurotransmitter Agents
Age Groups
Stroke
Neurons
Brain
Proteins

Keywords

  • Aging
  • GLAST
  • GLT-1
  • Striatum
  • Voltammetry
  • l-Glutamate

Cite this

Nickell, Justin ; Salvatore, Michael Francis ; Pomerleau, Francois ; Apparsundaram, Subbu ; Gerhardt, Greg A. / Reduced plasma membrane surface expression of GLAST mediates decreased glutamate regulation in the aged striatum. In: Neurobiology of Aging. 2007 ; Vol. 28, No. 11. pp. 1737-1748.
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Reduced plasma membrane surface expression of GLAST mediates decreased glutamate regulation in the aged striatum. / Nickell, Justin; Salvatore, Michael Francis; Pomerleau, Francois; Apparsundaram, Subbu; Gerhardt, Greg A.

In: Neurobiology of Aging, Vol. 28, No. 11, 01.11.2007, p. 1737-1748.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Salvatore, Michael Francis

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