Defective dentate nucleus GABA receptors in essential tremor.
Identifieur interne : 001255 ( Main/Exploration ); précédent : 001254; suivant : 001256Defective dentate nucleus GABA receptors in essential tremor.
Auteurs : Sarah Paris-Robidas [Canada] ; Elodie Brochu ; Marion Sintes ; Vincent Emond ; Mélanie Bousquet ; Milène Vandal ; Mireille Pilote ; Cyntia Tremblay ; Thérèse Di Paolo ; Ali H. Rajput ; Alex Rajput ; Frédéric CalonSource :
- Brain : a journal of neurology [ 1460-2156 ] ; 2012.
English descriptors
- KwdEn :
- Aged, Aged, 80 and over, Autoradiography, Cerebellar Nuclei (metabolism), Essential Tremor (genetics), Essential Tremor (metabolism), Female, Humans, Male, Parkinson Disease (genetics), Parkinson Disease (metabolism), Receptors, GABA-A (genetics), Receptors, GABA-A (metabolism), Receptors, GABA-B (genetics), Receptors, GABA-B (metabolism).
- MESH :
- chemical , genetics : Receptors, GABA-A, Receptors, GABA-B.
- genetics : Essential Tremor, Parkinson Disease.
- metabolism : Cerebellar Nuclei, Essential Tremor, Parkinson Disease, Receptors, GABA-A, Receptors, GABA-B.
- Aged, Aged, 80 and over, Autoradiography, Female, Humans, Male.
Abstract
The development of new treatments for essential tremor, the most frequent movement disorder, is limited by a poor understanding of its pathophysiology and the relative paucity of clinicopathological studies. Here, we report a post-mortem decrease in GABA(A) (35% reduction) and GABA(B) (22-31% reduction) receptors in the dentate nucleus of the cerebellum from individuals with essential tremor, compared with controls or individuals with Parkinson's disease, as assessed by receptor-binding autoradiography. Concentrations of GABA(B) receptors in the dentate nucleus were inversely correlated with the duration of essential tremor symptoms (r(2) = 0.44, P < 0.05), suggesting that the loss of GABA(B) receptors follows the progression of the disease. In situ hybridization experiments also revealed a diminution of GABA(B(1a+b)) receptor messenger RNA in essential tremor (↓27%). In contrast, no significant changes of GABA(A) and GABA(B) receptors (protein and messenger RNA), GluN2B receptors, cytochrome oxidase-1 or GABA concentrations were detected in molecular or granular layers of the cerebellar cortex. It is proposed that a decrease in GABA receptors in the dentate nucleus results in disinhibition of cerebellar pacemaker output activity, propagating along the cerebello-thalamo-cortical pathways to generate tremors. Correction of such defective cerebellar GABAergic drive could have a therapeutic effect in essential tremor.
DOI: 10.1093/brain/awr301
PubMed: 22120148
Affiliations:
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Le document en format XML
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Rajput</name></author><author><name sortKey="Rajput, Alex" sort="Rajput, Alex" uniqKey="Rajput A" first="Alex" last="Rajput">Alex Rajput</name></author><author><name sortKey="Calon, Frederic" sort="Calon, Frederic" uniqKey="Calon F" first="Frédéric" last="Calon">Frédéric Calon</name></author></analytic><series><title level="j">Brain : a journal of neurology</title><idno type="eISSN">1460-2156</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Autoradiography</term><term>Cerebellar Nuclei (metabolism)</term><term>Essential Tremor (genetics)</term><term>Essential Tremor (metabolism)</term><term>Female</term><term>Humans</term><term>Male</term><term>Parkinson Disease (genetics)</term><term>Parkinson Disease (metabolism)</term><term>Receptors, GABA-A (genetics)</term><term>Receptors, GABA-A (metabolism)</term><term>Receptors, GABA-B (genetics)</term><term>Receptors, GABA-B (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Receptors, GABA-A</term><term>Receptors, GABA-B</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Essential Tremor</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Cerebellar Nuclei</term><term>Essential Tremor</term><term>Parkinson Disease</term><term>Receptors, GABA-A</term><term>Receptors, GABA-B</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Autoradiography</term><term>Female</term><term>Humans</term><term>Male</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The development of new treatments for essential tremor, the most frequent movement disorder, is limited by a poor understanding of its pathophysiology and the relative paucity of clinicopathological studies. Here, we report a post-mortem decrease in GABA(A) (35% reduction) and GABA(B) (22-31% reduction) receptors in the dentate nucleus of the cerebellum from individuals with essential tremor, compared with controls or individuals with Parkinson's disease, as assessed by receptor-binding autoradiography. Concentrations of GABA(B) receptors in the dentate nucleus were inversely correlated with the duration of essential tremor symptoms (r(2) = 0.44, P < 0.05), suggesting that the loss of GABA(B) receptors follows the progression of the disease. In situ hybridization experiments also revealed a diminution of GABA(B(1a+b)) receptor messenger RNA in essential tremor (↓27%). In contrast, no significant changes of GABA(A) and GABA(B) receptors (protein and messenger RNA), GluN2B receptors, cytochrome oxidase-1 or GABA concentrations were detected in molecular or granular layers of the cerebellar cortex. It is proposed that a decrease in GABA receptors in the dentate nucleus results in disinhibition of cerebellar pacemaker output activity, propagating along the cerebello-thalamo-cortical pathways to generate tremors. Correction of such defective cerebellar GABAergic drive could have a therapeutic effect in essential tremor.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Bousquet, Melanie" sort="Bousquet, Melanie" uniqKey="Bousquet M" first="Mélanie" last="Bousquet">Mélanie Bousquet</name><name sortKey="Brochu, Elodie" sort="Brochu, Elodie" uniqKey="Brochu E" first="Elodie" last="Brochu">Elodie Brochu</name><name sortKey="Calon, Frederic" sort="Calon, Frederic" uniqKey="Calon F" first="Frédéric" last="Calon">Frédéric Calon</name><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Thérèse" last="Di Paolo">Thérèse Di Paolo</name><name sortKey="Emond, Vincent" sort="Emond, Vincent" uniqKey="Emond V" first="Vincent" last="Emond">Vincent Emond</name><name sortKey="Pilote, Mireille" sort="Pilote, Mireille" uniqKey="Pilote M" first="Mireille" last="Pilote">Mireille Pilote</name><name sortKey="Rajput, Alex" sort="Rajput, Alex" uniqKey="Rajput A" first="Alex" last="Rajput">Alex Rajput</name><name sortKey="Rajput, Ali H" sort="Rajput, Ali H" uniqKey="Rajput A" first="Ali H" last="Rajput">Ali H. Rajput</name><name sortKey="Sintes, Marion" sort="Sintes, Marion" uniqKey="Sintes M" first="Marion" last="Sintes">Marion Sintes</name><name sortKey="Tremblay, Cyntia" sort="Tremblay, Cyntia" uniqKey="Tremblay C" first="Cyntia" last="Tremblay">Cyntia Tremblay</name><name sortKey="Vandal, Milene" sort="Vandal, Milene" uniqKey="Vandal M" first="Milène" last="Vandal">Milène Vandal</name></noCountry><country name="Canada"><noRegion><name sortKey="Paris Robidas, Sarah" sort="Paris Robidas, Sarah" uniqKey="Paris Robidas S" first="Sarah" last="Paris-Robidas">Sarah Paris-Robidas</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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