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Neuroprotection by Lowering Cholesterol

  • Tatiana Borisova
Chapter
Part of the SpringerBriefs in Neuroscience book series (BRIEFSNEUROSCI, volume 12)

Abstract

In stroke, cerebral hypoxia/ischemia, and traumatic brain injury, the development of neurotoxocity is provoked by enhanced extracellular glutamate, which is released from nerve cells mainly by glutamate transporter reversal—a distinctive feature of these pathological states. Transporter-mediated glutamate release from the synaptosomes: (1) stimulated by depolarization of the plasma membrane; (2) by means of heteroexchange with competitive transportable inhibitor of glutamate transporters DL-threo-β-hydroxyaspartate; (3) in low-[Na+] medium; and (4) during dissipation of the proton gradient of synaptic vesicles by the protonophore FCCP; was decreased under conditions of cholesterol deficiency by approximately 24, 28, 40, 17%, respectively.

A decrease in the level of membrane cholesterol attenuated transporter-mediated glutamate release from nerve terminals. Therefore, lowering cholesterol may be used in neuroprotection in stroke, ischemia, and traumatic brain injury that are associated with an increase in glutamate uptake reversal. This data can explain the neuroprotective effects of statins in these pathological states and provide one of the mechanisms of their neuroprotective action. However, besides these disorders lowering cholesterol may cause harmful consequences decreasing glutamate uptake by nerve terminals.

Keywords

Traumatic Brain Injury Synaptic Vesicle Nerve Terminal Glutamate Release Glutamate Transporter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Tatiana Borisova
    • 1
  1. 1.Department of Neurochemistry Palladin Institute of BiochemistryNational Academy of Sciences of UkraineKievUkraine

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