1Psychiatry Res 2014 Nov 219: 674-9
TitleExpression profile of neurotransmitter receptor and regulatory genes in the prefrontal cortex of spontaneously hypertensive rats: relevance to neuropsychiatric disorders.
AbstractThe 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.
SCZ Keywordsschizophrenia
2PLoS ONE 2015 -1 10: e0125116
TitlePharmacological Characterisation of Nicotinic Acetylcholine Receptors Expressed in Human iPSC-Derived Neurons.
AbstractNeurons derived from human induced pluripotent stem cells (iPSCs) represent a potentially valuable tool for the characterisation of neuronal receptors and ion channels. Previous studies on iPSC-derived neuronal cells have reported the functional characterisation of a variety of receptors and ion channels, including glutamate receptors, ?-aminobutyric acid (GABA) receptors and several voltage-gated ion channels. In the present study we have examined the expression and functional properties of nicotinic acetylcholine receptors (nAChRs) in human iPSC-derived neurons. Gene expression analysis indicated the presence of transcripts encoding several nAChR subunits, with highest levels detected for ?3-?7, ?1, ?2 and ?4 subunits (encoded by CHRNA3-CHRNA7, CHRNB1, CHRNB2 and CHRNB4 genes). In addition, similarly high transcript levels were detected for the truncated dup?7 subunit transcript, encoded by the partially duplicated gene CHRFAM7A, which has been associated with psychiatric disorders such as schizophrenia. The functional properties of these nAChRs have been examined by calcium fluorescence and by patch-clamp recordings. The data obtained suggest that the majority of functional nAChRs expressed in these cells have pharmacological properties typical of ?7 receptors. Large responses were induced by a selective ?7 agonist (compound B), in the presence of the ?7-selective positive allosteric modulator (PAM) PNU-120596, which were blocked by the ?7-selective antagonist methyllycaconitine (MLA). In addition, a small proportion of the neurons express nAChRs with properties typical of heteromeric (non-?7 containing) nAChR subtypes. These cells therefore represent a great tool to advance our understanding of the properties of native human nAChRs, ?7 in particular.
SCZ Keywordsschizophrenia