The GABA Hypothesis in Essential Tremor

The gamma-aminobutyric acid (GABA) hypothesis in essential tremor (ET) implies a disturbance of the GABAergic system, especially involving the cerebellum. This review examines the evidence of the GABA hypothesis. The review is based on published data about GABA dysfunction in ET, taking into account...

ver descrição completa

Detalhes bibliográficos
Autor: Gironell, Alexandre|||0000-0003-2109-9030
Tipo de documento: artigo
Data de publicação:2014
País:España
Recursos:Universitat Autònoma de Barcelona
Repositório:Dipòsit Digital de Documents de la UAB
Idioma:inglês
OAI Identifier:oai:ddd.uab.cat:185081
Acesso em linha:https://ddd.uab.cat/record/185081
https://dx.doi.org/urn:doi:10.7916/D8SF2T9C
Access Level:Acceso aberto
Palavra-chave:Essential tremor
GABA
Gamma-aminobutyric acid
id ES_4d6d52aec8b9977503f8c4a7ebb2af44
oai_identifier_str oai:ddd.uab.cat:185081
network_acronym_str ES
network_name_str España
repository_id_str
spelling The GABA Hypothesis in Essential TremorLights and ShadowsGironell, Alexandre|||0000-0003-2109-9030Essential tremorGABAGamma-aminobutyric acidThe gamma-aminobutyric acid (GABA) hypothesis in essential tremor (ET) implies a disturbance of the GABAergic system, especially involving the cerebellum. This review examines the evidence of the GABA hypothesis. The review is based on published data about GABA dysfunction in ET, taking into account studies on cerebrospinal fluid, pathology, electrophysiology, genetics, neuroimaging, experimental animal models, and human drug therapies. Findings from several studies support the GABA hypothesis in ET. The hypothesis follows four steps: 1) cerebellar neurodegeneration with Purkinje cell loss; 2) a decrease in GABA system activity in deep cerebellar neurons; 3) disinhibition in output deep cerebellar neurons with pacemaker activity; and 4) an increase in rhythmic activity of the thalamus and thalamo-cortical circuit, contributing to the generation of tremor. Doubts have been cast on this hypothesis, however, by the fact that it is based on relatively few works, controversial post-mortem findings, and negative genetic studies on the GABA system. Furthermore, GABAergic drug efficacy is low and some GABAergic drugs do not have antitremoric efficacy. The GABA hypothesis continues to be the most robust pathophysiological hypothesis to explain ET. There is light in all GABA hypothesis steps, but a number of shadows cannot be overlooked. We need more studies to clarify the neurodegenerative nature of the disease, to confirm the decrease of GABA activity in the cerebellum, and to test more therapies that enhance the GABA transmission specifically in the cerebellum area.Universitat Autònoma de Barcelona 22014-01-0120142014-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/185081https://dx.doi.org/urn:doi:10.7916/D8SF2T9Creponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1850812026-06-06T12:50:31Z
dc.title.none.fl_str_mv The GABA Hypothesis in Essential Tremor
Lights and Shadows
title The GABA Hypothesis in Essential Tremor
spellingShingle The GABA Hypothesis in Essential Tremor
Gironell, Alexandre|||0000-0003-2109-9030
Essential tremor
GABA
Gamma-aminobutyric acid
title_short The GABA Hypothesis in Essential Tremor
title_full The GABA Hypothesis in Essential Tremor
title_fullStr The GABA Hypothesis in Essential Tremor
title_full_unstemmed The GABA Hypothesis in Essential Tremor
title_sort The GABA Hypothesis in Essential Tremor
dc.creator.none.fl_str_mv Gironell, Alexandre|||0000-0003-2109-9030
author Gironell, Alexandre|||0000-0003-2109-9030
author_facet Gironell, Alexandre|||0000-0003-2109-9030
author_role author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Essential tremor
GABA
Gamma-aminobutyric acid
topic Essential tremor
GABA
Gamma-aminobutyric acid
description The gamma-aminobutyric acid (GABA) hypothesis in essential tremor (ET) implies a disturbance of the GABAergic system, especially involving the cerebellum. This review examines the evidence of the GABA hypothesis. The review is based on published data about GABA dysfunction in ET, taking into account studies on cerebrospinal fluid, pathology, electrophysiology, genetics, neuroimaging, experimental animal models, and human drug therapies. Findings from several studies support the GABA hypothesis in ET. The hypothesis follows four steps: 1) cerebellar neurodegeneration with Purkinje cell loss; 2) a decrease in GABA system activity in deep cerebellar neurons; 3) disinhibition in output deep cerebellar neurons with pacemaker activity; and 4) an increase in rhythmic activity of the thalamus and thalamo-cortical circuit, contributing to the generation of tremor. Doubts have been cast on this hypothesis, however, by the fact that it is based on relatively few works, controversial post-mortem findings, and negative genetic studies on the GABA system. Furthermore, GABAergic drug efficacy is low and some GABAergic drugs do not have antitremoric efficacy. The GABA hypothesis continues to be the most robust pathophysiological hypothesis to explain ET. There is light in all GABA hypothesis steps, but a number of shadows cannot be overlooked. We need more studies to clarify the neurodegenerative nature of the disease, to confirm the decrease of GABA activity in the cerebellum, and to test more therapies that enhance the GABA transmission specifically in the cerebellum area.
publishDate 2014
dc.date.none.fl_str_mv 2
2014-01-01
2014
2014-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/185081
https://dx.doi.org/urn:doi:10.7916/D8SF2T9C
url https://ddd.uab.cat/record/185081
https://dx.doi.org/urn:doi:10.7916/D8SF2T9C
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869407690866819072
score 15,198674

Registros relacionados