Deep brain stimulation results in local glutamate and adenosine release: Investigation into the role of astrocytes

Vivianne L. Tawfik, Su-Youne Chang, Frederick L. Hitti, David W. Roberts, James C. Leiter, Svetlana Jovanovic, Kendall H Lee

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

BACKGROUND: Several neurological disorders are treated with deep brain stimulation; however, the mechanism underlying its ability to abolish oscillatory phenomena associated with diseases as diverse as Parkinson's disease and epilepsy remain largely unknown. OBJECTIVE: To investigate the role of specific neurotransmitters in deep brain stimulation and determine the role of non-neuronal cells in its mechanism of action. METHODS: We used the ferret thalamic slice preparation in vitro, which exhibits spontaneous spindle oscillations, to determine the effect of high-frequency stimulation on neurotransmitter release. We then performed experiments using an in vitro astrocyte culture to investigate the role of glial transmitter release in high-frequency stimulation-mediated abolishment of spindle oscillations. RESULTS: In this series of experiments, we demonstrated that glutamate and adenosine release in ferret slices was able to abolish spontaneous spindle oscillations. The glutamate release was still evoked in the presence of the Na channel blocker tetrodotoxin, but was eliminated with the vesicular H +-ATPase inhibitor bafilomycin and the calcium chelator 2-bis(2-aminophenoxy)-ethane-N,N,N′,N′-tetraacetic acid tetrakis acetoxymethyl ester. Furthermore, electrical stimulation of purified primary astrocytic cultures was able to evoke intracellular calcium transients and glutamate release, and bath application of 2-bis (2-aminophenoxy)-ethane-N,N, N′,N′-tetraacetic acid tetrakis acetoxymethyl ester inhibited glutamate release in this setting. CONCLUSION: Vesicular astrocytic neurotransmitter release may be an important mechanism by which deep brain stimulation is able to achieve clinical benefits.

Original languageEnglish (US)
Pages (from-to)367-375
Number of pages9
JournalNeurosurgery
Volume67
Issue number2
DOIs
StatePublished - Aug 2010

Fingerprint

Deep Brain Stimulation
Astrocytes
Adenosine
Glutamic Acid
Neurotransmitter Agents
Ferrets
Ethane
Esters
Acids
Proton-Translocating ATPases
Tetrodotoxin
Nervous System Diseases
Baths
Neuroglia
Electric Stimulation
Parkinson Disease
Epilepsy
Calcium
In Vitro Techniques

Keywords

  • Adenosine
  • Astrocytes
  • Deep brain stimulation
  • Glia
  • Glutamate
  • High-frequency stimulation

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Deep brain stimulation results in local glutamate and adenosine release : Investigation into the role of astrocytes. / Tawfik, Vivianne L.; Chang, Su-Youne; Hitti, Frederick L.; Roberts, David W.; Leiter, James C.; Jovanovic, Svetlana; Lee, Kendall H.

In: Neurosurgery, Vol. 67, No. 2, 08.2010, p. 367-375.

Research output: Contribution to journalArticle

Tawfik, Vivianne L. ; Chang, Su-Youne ; Hitti, Frederick L. ; Roberts, David W. ; Leiter, James C. ; Jovanovic, Svetlana ; Lee, Kendall H. / Deep brain stimulation results in local glutamate and adenosine release : Investigation into the role of astrocytes. In: Neurosurgery. 2010 ; Vol. 67, No. 2. pp. 367-375.
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