Metabotropic Glutamate Receptor 2 and Dopamine Receptor 2 Gene Expression Predict Sensorimotor Gating Response in the Genetically Heterogeneous NIH-HS Rat Strain
Østerbøg, Tina Becher (Research Laboratory for Stereology and Neuroscience. Bispebjerg and Frederiksberg Hospitals. Copenhagen)
On, Doan Minh (Department of Physiology and Biophysics. Virginia Commonwealth University School of Medicine)
Oliveras, Ignasi (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Río-Álamos, Cristobal (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Sánchez González, Ana (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Tapias-Espinosa, Carles (Departamento de Psiquiatría y Medicina Legal.)
Tobeña, Adolf 1950- (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Gonzalez-Maeso, Javier (Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine)
Fernández-Teruel, Alberto (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Aznar, Susana (Bispebjerg and Frederiksberg Hospitals (Copenhagen, Dinamarca))

Data:	2020
Resum:	Disruption of sensorimotor gating causes "flooding" of irrelevant sensory input and is considered a congenital trait in several neurodevelopmental disorders. Prepulse inhibition of acoustic startle response (PPI) is the operational measurement and has a high translational validity. Pharmacological studies in rodents have linked alterations in serotonin, dopamine and glutamate signalling to PPI disruption. How PPI response is associated with gene expression levels of these receptors is unknown. PPI response was assessed in 39 genetically heterogeneous National Institutes of Health-Heterogeneous Stock (NIH-HS) rats. Animals were classified as high, medium or low PPI. Expression levels of glutamate metabotropic receptor 2 (Grm2), dopamine receptor D2 (Drd2), dopamine receptor D1 (Drd1), serotonin receptor 1A (Htr1a), serotonin receptor 2A (Htr2a) and homer scaffolding protein 1 (Homer1) were investigated in prefrontal cortex (PFC) and striatum (STR). When comparing the two extreme phenotypes, only Drd2 in STR showed increased expression in the low PPI group. A multinomial model fitting all genes and all groups indicated that Grm2 in PFC, and Grm2 and Drd2 in the STR predicted PPI group. This was corroborated by a linear relationship of Grm2 with PPI in PFC, and Drd2 with PPI in STR. An interaction between levels of H3K27 trimethylation, associated with transcriptional repression, and PPI phenotype was observed for Drd2 in STR. Gene set enrichment analysis on a microarray dataset on Lewis rats confirmed enrichment of Drd2 in PFC in relation to PPI. These findings contribute to the understanding of the genetic substrate behind alterations in sensorimotor gating, relevant for its linkage to neurodevelopmental disorders.
Ajuts:	Agencia Estatal de Investigación PSI2017-82257-P Agència de Gestió d'Ajuts Universitaris i de Recerca 2014SGR-1587
Nota:	Altres ajuts: Foundation for the National Institutes of Health, R01MH084894
Drets:	Tots els drets reservats.
Llengua:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Matèria:	Epigenetics ; Gene expression ; Neurotransmitter receptors ; Postsynapse ; Schizophrenia ; Sensorimotor gating response
Publicat a:	Molecular neurobiology, Vol. 57 Núm. 3 (March 2020) , p. 1516-1528, ISSN 1559-1182

DOI: 10.1007/s12035-019-01829-w

33 p, 1.2 MB

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