title: Expression profile of neurotransmitter receptor and regulatory genes in the prefrontal cortex of spontaneously hypertensive rats: relevance to neuropsychiatric disorders.
abstract: The spontaneously hypertensive rat (SHR) strain was shown to be a useful animal model to study several behavioral, pathophysiological and pharmacological aspects of schizophrenia and attention-deficit/hyperactivity disorder. To further understand the genetic underpinnings of this model, our primary goal in this study was to compare the gene expression profile of neurotransmitter receptors and regulators in the prefrontal cortex (PFC) and nucleus accumbens (NAcc) of SHR and Wistar rats (control group). In addition, we investigated DNA methylation pattern of promoter region of the genes differentially expressed. We performed gene expression analysis using a PCRarray technology, which simultaneously measures the expression of 84 genes related to neurotransmission. Four genes were significantly downregulated in the PFC of SHR compared to Wistar rats (Gad2, Chrnb4, Slc5a7, and Qrfpr) and none in nucleus accumbens. Gad2 and Qrfpr have CpG islands in their promoter region. For both, the promoter region was hypomethylated in SHR group, and probably this mechanism is not related with the downregulation of these genes. In summary, we identified genes that are downregulated in the PFC of SHR, and might be related to the behavioral abnormalities exhibited by this strain.
authors.affiliation: Genetics Division, Department of Morphology and Genetics, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil; Interdisciplinary Laboratory of Clinical Neurosciences (LiNC), Sao Paulo, Brazil.
authors.forename: Marcos Leite
authors.initials: ML
authors.lastname: Santoro
authors.affiliation: Interdisciplinary Laboratory of Clinical Neurosciences (LiNC), Sao Paulo, Brazil; Department of Psychiatry, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Camila Maurício
authors.initials: CM
authors.lastname: Santos
authors.affiliation: Genetics Division, Department of Morphology and Genetics, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil; Interdisciplinary Laboratory of Clinical Neurosciences (LiNC), Sao Paulo, Brazil.
authors.forename: Vanessa Kiyomi
authors.initials: VK
authors.lastname: Ota
authors.affiliation: Interdisciplinary Laboratory of Clinical Neurosciences (LiNC), Sao Paulo, Brazil; Department of Psychiatry, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Ary
authors.initials: A
authors.lastname: Gadelha
authors.affiliation: Department of Biophysics and Investigation Center for Gene Therapy, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Roberta Sessa
authors.initials: RS
authors.lastname: Stilhano
authors.affiliation: Interdisciplinary Laboratory of Clinical Neurosciences (LiNC), Sao Paulo, Brazil; Department of Pharmacology, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Mariana Cepollaro
authors.initials: MC
authors.lastname: Diana
authors.affiliation: Genetics Division, Department of Morphology and Genetics, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil; Department of Psychiatry, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Patrícia Natália
authors.initials: PN
authors.lastname: Silva
authors.affiliation: Genetics Division, Department of Morphology and Genetics, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Letícia Maria Nery
authors.initials: LM
authors.lastname: Spíndola
authors.affiliation: Genetics Division, Department of Morphology and Genetics, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Melaragno
authors.affiliation: Interdisciplinary Laboratory of Clinical Neurosciences (LiNC), Sao Paulo, Brazil; Department of Psychiatry, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Rodrigo Affonseca
authors.initials: RA
authors.lastname: Bressan
authors.affiliation: Department of Biophysics and Investigation Center for Gene Therapy, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Han
authors.affiliation: Interdisciplinary Laboratory of Clinical Neurosciences (LiNC), Sao Paulo, Brazil; Department of Pharmacology, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil.
authors.forename: Vanessa Costhek
authors.initials: VC
authors.lastname: Abílio
authors.affiliation: Genetics Division, Department of Morphology and Genetics, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil; Interdisciplinary Laboratory of Clinical Neurosciences (LiNC), Sao Paulo, Brazil; Department of Psychiatry, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil. Electronic address: sinbelangero@gmail.com.
authors.forename: Sintia Iole
authors.initials: SI
authors.lastname: Belangero
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000378:metabolism* / Q000523:psychology*; D018899:CpG Islands; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D015870:Gene Expression; D005968:Glutamate Decarboxylase; D008297:Male; D009419:Nerve Tissue Proteins; D009714:Nucleus Accumbens / Q000378:metabolism* / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter / Q000235:genetics*; D011978:Receptors, Nicotinic; D027981:Symporters; D009435:Synaptic Transmission
chemical_list: C486720:Chrnb4 protein, mouse; D009419:Nerve Tissue Proteins; C516486:Qrfpr protein, rat; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; D011978:Receptors, Nicotinic; C510731:SLC5A7 protein, human; D027981:Symporters; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2
keywords: Chrnb4; DNA methylation; Gad2; Gene expression; Qrfpr; Slc5a7; Spontaneously hypertensive rats