Central relaxin-3 receptor (RXFP3) activation increases ERK phosphorylation in septal cholinergic neurons and impairs spatial working memory.

Ver/ Abrir
Impacto


Metadatos
Mostrar el registro completo del ítemcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/36080
comunitat-uji-handle3:10234/36082
INVESTIGACIONMetadatos
Título
Central relaxin-3 receptor (RXFP3) activation increases ERK phosphorylation in septal cholinergic neurons and impairs spatial working memory.Autor (es)
Fecha de publicación
2016-05-05Editor
SpringerResumen
The medial septum/diagonal band (MS/DB) is a relay region connecting the hypothalamus and brainstem with the hippocampus, and both the MS/DB and dorsal/ventral hippocampus receive strong topographic GABA/peptidergic ... [+]
The medial septum/diagonal band (MS/DB) is a relay region connecting the hypothalamus and brainstem with the hippocampus, and both the MS/DB and dorsal/ventral hippocampus receive strong topographic GABA/peptidergic projections from the nucleus incertus of the pontine tegmentum. The neuropeptide relaxin-3, released by these neurons, is the cognate ligand for a Gi/o-protein-coupled receptor, RXFP3, which is highly expressed within the MS/DB, and both cholinergic and GABAergic neurons in this region of rat brain receive relaxin-3 positive terminals/boutons. Comprehensive in vitro studies have demonstrated that a range of cell signaling pathways can be altered by RXFP3 stimulation, including inhibition of forskolin-activated cAMP levels and activation of ERK phosphorylation. In this study we investigated whether intracerebroventricular (icv) injection of RXFP3-A2, a selective relaxin-3 receptor agonist, altered ERK phosphorylation levels in the MS/DB of adult male rats. In addition, we assessed the neurochemical phenotype of phosphorylated (p) ERK-positive neurons in MS/DB after RXFP3-A2 administration by dual-label immunostaining for pERK and key neuronal markers. RXFP3-A2 injection significantly increased pERK levels in MS/DB, compared to vehicle at 20 and 90 min post-injection. In addition, icv injection of RXFP3-A2 increased the number of cells expressing pERK in the MS/DB after 90 min, with increases detected in cholinergic, but not GABAergic neurons. Moreover, we found that septal cholinergic neurons express RXFP3 and that icv infusions of RXFP3-A2 impaired alternation in a spatial working memory behavioral paradigm. The presence of the receptor and the specific RXFP3-related activation of the MAPK/ERK pathway in MS/DB cholinergic neurons identifies them as a key target of ascending relaxin-3 projections with implications for the acute and chronic inhibition of cholinergic neuron activity/function by relaxin-3/RXFP3 signaling. [-]
Palabras clave / Materias
Cita bibliográfica
ALBERT GASCÓ, Héctor; GARCÍA AVILÉS, Álvaro; MOUSTAFA, S.; SÁNCHEZ SARASÚA DE LA BÁRCENA, Sandra; GUNDLANCH, Andrew L.; OLUCHA BORDONAU, Francisco E., SÁNCHEZ PÉREZ, Ana María. Central relaxin-3 receptor (RXFP3) activation increases ERK phosphorylation in septal cholinergic neurons and impairs spatial working memory. Brain structure & function (2016), online, pp. 1-15Tipo de documento
info:eu-repo/semantics/articleDerechos de acceso
info:eu-repo/semantics/openAccess
Aparece en las colecciones
- MED_Articles [246]