Modeling depression: social dominance–submission gene expression patterns in rat neocortex

Social defeat, a paradigm of depression in rats that elicits 22-kHz vocalizations, preferentially activates the cholinergic signaling pathway in the periaqueductal gray

“…Notwithstanding, in-house design and fabrication allows a stringent level of quality control, exquisite sensitivity, and economy that typically constrains the number of arrays required to conduct experiments with sufficient numbers of biological samples/replicates and provide statistically acceptable sensitivity and specificity. This approach has reliably identified transcripts having as low as 10% differences in transcript expression between RNA samples observed in heterogeneous tissue sources such as neocortex and hippocampus [41,56]. In sum, our approach of highly selective yet broad ontological coverage of the rat transcriptome facilitates the generation of high quality data from systems/paradigms sensitive to small regulatory changes that can be confirmed by independent measurements.…”

“…2.1.1 Subjects-The cohort of animals used in this study was previously described [41]. In sum, this research was approved by the Bowling Green State University IACUC.…”

“…Prior to analysis, brain samples were further dissected into nine sub-areas: 1) frontal cortex (FCTX, tissue anterior to the frontal pole of the basal ganglia); 2) posterior cortex (PCTX, including all the posterior neocortical areas dorsal to the rhinal sulcus behind the FCTX sample); 3*) basal ganglia (including caudate nuclei, globus pallidus and nucleus accumbens); 4*) temporal-amygdaloid area; 5*) hippocampus; 6*) diencephalon (including most of the thalamus and hypothalamus); 7*) the cerebellum, 8) the mesencephalon, containing the periaqueductal gray, and 9*) the brainstem (Note: for explanation of asterisks, see end of paragraph). The cortical areas were the focus of an earlier report [41]. For these studies, the PAG was isolated by taking a circular punch from a transverse section of mesencephalon extending from the meso-diencephalic juncture to the entry of the fourth ventricle.…”

“…We have recently identified several molecular pathways in neocortical tissue associated with the genesis of depression [41]. As part of our comprehensive molecular strategy, analysis of additional, critical brain regions will augment our ability to identify targetable molecular pathways relevant to the onset of depression, as well as the development of the next generation of more efficacious antidepressants.…”

“…mRNAs isolated from the periaqueductal gray regions were examined by microarray analysis. We utilized an integrated transcriptome profiling platform that coupled (1) design and fabrication of focused oligonucleotide microarrays containing a restricted number of transcripts carefully selected to provide near complete representation of the major rat ontological categories, with (2) stringent statistical and ontological analyses to identify relevant genesets, and (3) ultimate corroboration of the geneset by quantitative real-time PCR [41]. We have overcome the necessity for broad transcriptome coverage typically provided by global commercial arrays by the strategic selection of genes which are represented on our microarrays.…”