Journal ArticleDOI
Metabotropic Glutamate Receptor 2 and Dopamine Receptor 2 Gene Expression Predict Sensorimotor Gating Response in the Genetically Heterogeneous NIH-HS Rat Strain
Tina Becher Østerbøg,Doan Minh On,Ignasi Oliveras,Cristóbal Río-Álamos,Cristóbal Río-Álamos,Ana Sánchez-González,Carles Tapias-Espinosa,Adolf Tobeña,Javier González-Maeso,Alberto Fernández-Teruel,Susana Aznar +10 more
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TLDR
Gene set enrichment analysis on a microarray dataset on Lewis rats confirmed enrichment of Drd2 in PFC in relation to PPI, contributing to the understanding of the genetic substrate behind alterations in sensorimotor gating, relevant for its linkage to neurodevelopmental disorders.Abstract:
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.read more
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Journal ArticleDOI
Characterization of dopamine D2 receptor binding, expression and signaling in different brain regions of control and schizophrenia-model Wisket rats.
TL;DR: This study proved that the Wisket animals show altered D2 receptor expression and function which might be related to the schizophrenia-like symptoms.
Journal ArticleDOI
Modulation of mGlu5 improves sensorimotor gating deficits in rats neonatally treated with quinpirole through changes in dopamine D2 signaling.
TL;DR: In this paper, the positive allosteric modulator of metabotropic glutamate receptor type 5 (mGlu5) 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB) was analyzed whether the positive modulator would alleviate deficits in prepulse inhibition and affect dopamine (DA) D2 signaling in the dorsal striatum and prefrontal cortex (PFC) in the neonatal quinpirole (NQ) model of schizophrenia.
Journal ArticleDOI
Prepulse inhibition deficits in inbred and outbred rats and between-strain differences in startle habituation do not depend on startle reactivity levels
Ignasi Oliveras,Carles Tapias-Espinosa,Cristóbal Río-Álamos,Daniel Sampedro-Viana,Toni Cañete,Ana Sánchez-González,Adolf Tobeña,Alberto Fernández-Teruel +7 more
TL;DR: In this paper , the influence of baseline startle response on prepulse inhibition (PPI) was assessed in large samples of Roman high (RHA) and low-avoidance (RLA) rat strains and in genetically heterogeneous stock (HS) rats.
Journal ArticleDOI
Different maturation patterns for sensorimotor gating and startle habituation deficits in male and female RHA vs RLA rats
Ignasi Oliveras,OscarJ. Soria-Ruiz,Daniel Sampedro-Viana,Toni Cañete,Cristóbal Río-Álamos,Adolf Tobeña,Alberto Fernández-Teruel +6 more
TL;DR: In this article , the authors evaluated the levels of impaired prepulse inhibition (PPI) of both strains and both sexes during these three developmental phases and investigated the onset of startle habituation deficits in the same groups.
References
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Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles
Aravind Subramanian,Pablo Tamayo,Vamsi K. Mootha,Sayan Mukherjee,Benjamin L. Ebert,Michael A. Gillette,Amanda G. Paulovich,Scott L. Pomeroy,Todd R. Golub,Eric S. Lander,Jill P. Mesirov +10 more
TL;DR: The Gene Set Enrichment Analysis (GSEA) method as discussed by the authors focuses on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation.
Journal ArticleDOI
The Dopamine Hypothesis of Schizophrenia: Version III—The Final Common Pathway
Oliver D. Howes,Shitij Kapur +1 more
TL;DR: The dopamine hypothesis of schizophrenia-version III is synthesized into a comprehensive framework that links risk factors, including pregnancy and obstetric complications, stress and trauma, drug use, and genes, to increased presynaptic striatal dopaminergic function.
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Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review.
TL;DR: While the PPI model based on the effects of direct DA agonists is the most well-validated for the identification of known antipsychotic drugs, the isolation rearing model also appears to be sensitive to both typical and atypical antipsychotics, and the 5-HT P PI model is less generally sensitive to antippsychotic medications, but can provide insight into the contribution of serotonergic systems to the actions of newer antipsychosis that act upon multiple receptors.
Journal ArticleDOI
Prestimulus Effects on Human Startle Reflex in Normals and Schizophrenics
TL;DR: When 20 normal subjects were compared to 12 schizophrenic subjects, significant differences in eyeblink response were found for blink amplitude and latency in the 60 msec prestimulus condition, which is consistent with information processing “overload” theories of sensory overstimulation in schizophrenia.
Journal ArticleDOI
Charting histone modifications and the functional organization of mammalian genomes
Vicky Weijie Zhou,Alon Goren,Alon Goren,Alon Goren,Bradley E. Bernstein,Bradley E. Bernstein,Bradley E. Bernstein +6 more
TL;DR: A selection of recent studies that have probed histone modifications and successive layers of chromatin structure in mammalian genomes, the patterns that have been identified and future directions for research are reviewed.