Deep brain stimulation (DBS) is a widely used neurosurgical approach
to treating tremor and other movement disorders. In addition, the
use of DBS in a number of psychiatric diseases, including obsessive-compulsive
disorders and depression, is currently being tested. Despite the
rapid increase in the number of individuals with surgically implanted
stimulation electrodes, the cellular pathways involved in mediating
the effects of DBS remain unknown. Here we show that DBS is associated
with a marked increase in the release of ATP, resulting in accumulation
of its catabolic product, adenosine. Adenosine A1 receptor activation
depresses excitatory transmission in the thalamus and reduces both
tremor- and DBS-induced side effects. Intrathalamic infusion of A1
receptor agonists directly reduces tremor, whereas adenosine A1 receptor-null
mice show involuntary movements and seizure at stimulation intensities
below the therapeutic level. Furthermore, our data indicate that
endogenous adenosine mechanisms are active in tremor, thus supporting
the clinical notion that caffeine, a nonselective adenosine receptor
antagonist, can trigger or exacerbate essential tremor. Our findings
suggest that nonsynaptic mechanisms involving the activation of A1
receptors suppress tremor activity and limit stimulation-induced
side effects, thereby providing a new pharmacological target to replace
or improve the efficacy of DBS.
%0 Journal Article
%1 Bekar2008
%A Bekar, Lane
%A Libionka, Witold
%A Tian, Guo-Feng
%A Xu, Qiwu
%A Torres, Arnulfo
%A Wang, Xiaohai
%A Lovatt, Ditte
%A Williams, Erika
%A Takano, Takahiro
%A Schnermann, Jurgen
%A Bakos, Robert
%A Nedergaard, Maiken
%D 2008
%I Nature Publishing Group
%J Nature medicine
%K imported
%N 1
%P 75--80
%T Adenosine is crucial for deep brain stimulation-mediated attenuation
of tremor.
%U http://dx.doi.org/10.1038/nm1693
%V 14
%X Deep brain stimulation (DBS) is a widely used neurosurgical approach
to treating tremor and other movement disorders. In addition, the
use of DBS in a number of psychiatric diseases, including obsessive-compulsive
disorders and depression, is currently being tested. Despite the
rapid increase in the number of individuals with surgically implanted
stimulation electrodes, the cellular pathways involved in mediating
the effects of DBS remain unknown. Here we show that DBS is associated
with a marked increase in the release of ATP, resulting in accumulation
of its catabolic product, adenosine. Adenosine A1 receptor activation
depresses excitatory transmission in the thalamus and reduces both
tremor- and DBS-induced side effects. Intrathalamic infusion of A1
receptor agonists directly reduces tremor, whereas adenosine A1 receptor-null
mice show involuntary movements and seizure at stimulation intensities
below the therapeutic level. Furthermore, our data indicate that
endogenous adenosine mechanisms are active in tremor, thus supporting
the clinical notion that caffeine, a nonselective adenosine receptor
antagonist, can trigger or exacerbate essential tremor. Our findings
suggest that nonsynaptic mechanisms involving the activation of A1
receptors suppress tremor activity and limit stimulation-induced
side effects, thereby providing a new pharmacological target to replace
or improve the efficacy of DBS.
@article{Bekar2008,
abstract = {Deep brain stimulation (DBS) is a widely used neurosurgical approach
to treating tremor and other movement disorders. In addition, the
use of DBS in a number of psychiatric diseases, including obsessive-compulsive
disorders and depression, is currently being tested. Despite the
rapid increase in the number of individuals with surgically implanted
stimulation electrodes, the cellular pathways involved in mediating
the effects of DBS remain unknown. Here we show that DBS is associated
with a marked increase in the release of ATP, resulting in accumulation
of its catabolic product, adenosine. Adenosine A1 receptor activation
depresses excitatory transmission in the thalamus and reduces both
tremor- and DBS-induced side effects. Intrathalamic infusion of A1
receptor agonists directly reduces tremor, whereas adenosine A1 receptor-null
mice show involuntary movements and seizure at stimulation intensities
below the therapeutic level. Furthermore, our data indicate that
endogenous adenosine mechanisms are active in tremor, thus supporting
the clinical notion that caffeine, a nonselective adenosine receptor
antagonist, can trigger or exacerbate essential tremor. Our findings
suggest that nonsynaptic mechanisms involving the activation of A1
receptors suppress tremor activity and limit stimulation-induced
side effects, thereby providing a new pharmacological target to replace
or improve the efficacy of DBS.},
added-at = {2011-03-27T17:20:41.000+0200},
author = {Bekar, Lane and Libionka, Witold and Tian, Guo-Feng and Xu, Qiwu and Torres, Arnulfo and Wang, Xiaohai and Lovatt, Ditte and Williams, Erika and Takano, Takahiro and Schnermann, Jurgen and Bakos, Robert and Nedergaard, Maiken},
biburl = {https://www.bibsonomy.org/bibtex/23f14307a0a10105e64175c1116fd1ca4/yevb0},
interhash = {fd14694a38a53c24de37e03744fdbe21},
intrahash = {3f14307a0a10105e64175c1116fd1ca4},
journal = {Nature medicine},
keywords = {imported},
month = jan,
number = 1,
pages = {75--80},
publisher = {Nature Publishing Group},
shorttitle = {Nat Med},
timestamp = {2011-03-27T17:20:44.000+0200},
title = {Adenosine is crucial for deep brain stimulation-mediated attenuation
of tremor.},
url = {http://dx.doi.org/10.1038/nm1693},
volume = 14,
year = 2008
}