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


CONCLUSIONS
Vesicular astrocytic neurotransmitter release may be an important mechanism by which deep brain stimulation is able to achieve clinical benefits.
Tawfik
Vivianne L
VL
Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire, USA.
Chang
Su-Youne
SY
Hitti
Frederick L
FL
Roberts
David W
DW
Leiter
James C
JC
Jovanovic
Svetlana
S
Lee
Kendall H
KH
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001923:Brain Chemistry / Q000528:radiation effects*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D046690:Deep Brain Stimulation; D004558:Electric Stimulation; D004563:Electrochemistry; D055724:Electrophysiological Phenomena; D005289:Ferrets; D018698:Glutamic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009415:Nerve Net / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013788:Thalamus / Q000502:physiology
D018377:Neurotransmitter Agents; D026941:Sodium Channel Blockers; D018698:Glutamic Acid; D013779:Tetrodotoxin; D000241:Adenosine; D002118:Calcium