Balance of Go1α and Go2α expression regulates motor function via the striatal dopaminergic system

Abstract: The heterotrimeric G-protein Go with its splice variants, Go1α and Go2α, seems to be involved in the regulation of motor function but isoform-specific effects are still unclear. We found that Go1α-/- knockouts performed worse on the rota-rod than Go2α-/- and wild-type (WT) mice. In Go1+2α-...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Baron, Jens, Bilbao, Ainhoa, Hörtnagl, Heide, Birnbaumer, Lutz, Leixner, Sarah, Spanagel, Rainer, Ahnert-Hilger, Gudrun, Brunk, Irene
Otros Autores: 0000-0002-3301-2628
Formato: Artículo
Lenguaje:Inglés
Publicado: Wiley 2019
Materias:
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/8694
Aporte de:
id I33-R139123456789-8694
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic MOTRICIDAD
COCAINA
COMPORTAMIENTO
MOTIVACION
spellingShingle MOTRICIDAD
COCAINA
COMPORTAMIENTO
MOTIVACION
Baron, Jens
Bilbao, Ainhoa
Hörtnagl, Heide
Birnbaumer, Lutz
Leixner, Sarah
Spanagel, Rainer
Ahnert-Hilger, Gudrun
Brunk, Irene
Balance of Go1α and Go2α expression regulates motor function via the striatal dopaminergic system
topic_facet MOTRICIDAD
COCAINA
COMPORTAMIENTO
MOTIVACION
description Abstract: The heterotrimeric G-protein Go with its splice variants, Go1α and Go2α, seems to be involved in the regulation of motor function but isoform-specific effects are still unclear. We found that Go1α-/- knockouts performed worse on the rota-rod than Go2α-/- and wild-type (WT) mice. In Go1+2α-/- mice motor function was partially recovered. Furthermore, Go1+2α-/- mice showed an increased spontaneous motor activity. Compared to wild types or Go2α-/- mice, Go1+2α-/- mice developed increased behavioural sensitization following repetitive cocaine treatment, but failed to develop conditioned place preference. Analysis of dopamine concentration and expression of D1 and D2 receptors unravelled splice-variant-specific imbalances in the striatal dopaminergic system: In Go1α-/- mice dopamine concentration and vesicular monoamine uptake were increased compared to wild types. The expression of the D2 receptor was higher in Go1α-/- compared to wild type littermates, but unchanged in Go2α-/- mice. Deletion of both Go1α and Go2α re-established both dopamine and D2 receptor levels comparable to those in the wild-type. Cocaine treatment had no effect on the ratio of D1 receptor to D2 receptor in Go1+2α-/- mutants, but decreased this ratio in Go2α-/- mice. Finally, we observed that the deletion of Go1α led to a threefold higher striatal expression of Go2α. Taken together our data suggest that a balance in the expression of Go1α and Go2α sustains normal motor function. Deletion of either splice variant results in divergent behavioural and molecular alterations in the striatal dopaminergic system. Deletion of both splice variants partially restores the behavioural and molecular changes.
author2 0000-0002-3301-2628
author_facet 0000-0002-3301-2628
Baron, Jens
Bilbao, Ainhoa
Hörtnagl, Heide
Birnbaumer, Lutz
Leixner, Sarah
Spanagel, Rainer
Ahnert-Hilger, Gudrun
Brunk, Irene
format Artículo
author Baron, Jens
Bilbao, Ainhoa
Hörtnagl, Heide
Birnbaumer, Lutz
Leixner, Sarah
Spanagel, Rainer
Ahnert-Hilger, Gudrun
Brunk, Irene
author_sort Baron, Jens
title Balance of Go1α and Go2α expression regulates motor function via the striatal dopaminergic system
title_short Balance of Go1α and Go2α expression regulates motor function via the striatal dopaminergic system
title_full Balance of Go1α and Go2α expression regulates motor function via the striatal dopaminergic system
title_fullStr Balance of Go1α and Go2α expression regulates motor function via the striatal dopaminergic system
title_full_unstemmed Balance of Go1α and Go2α expression regulates motor function via the striatal dopaminergic system
title_sort balance of go1α and go2α expression regulates motor function via the striatal dopaminergic system
publisher Wiley
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/8694
work_keys_str_mv AT baronjens balanceofgo1aandgo2aexpressionregulatesmotorfunctionviathestriataldopaminergicsystem
AT bilbaoainhoa balanceofgo1aandgo2aexpressionregulatesmotorfunctionviathestriataldopaminergicsystem
AT hortnaglheide balanceofgo1aandgo2aexpressionregulatesmotorfunctionviathestriataldopaminergicsystem
AT birnbaumerlutz balanceofgo1aandgo2aexpressionregulatesmotorfunctionviathestriataldopaminergicsystem
AT leixnersarah balanceofgo1aandgo2aexpressionregulatesmotorfunctionviathestriataldopaminergicsystem
AT spanagelrainer balanceofgo1aandgo2aexpressionregulatesmotorfunctionviathestriataldopaminergicsystem
AT ahnerthilgergudrun balanceofgo1aandgo2aexpressionregulatesmotorfunctionviathestriataldopaminergicsystem
AT brunkirene balanceofgo1aandgo2aexpressionregulatesmotorfunctionviathestriataldopaminergicsystem
bdutipo_str Repositorios
_version_ 1764820528452861952