Abstract
We used whole human genome microarray screening of highly enriched neuronal populations from two thalamic regions in postmortem samples from subjects with schizophrenia and controls to identify brain region-specific gene expression changes and possible transcriptional targets. The thalamic anterior nucleus is reciprocally connected to anterior cingulate, a schizophrenia-affected cortical region, and is also thought to be schizophrenia affected; the other thalamic region is not. Using two regions in the same subject to identify disease-relevant gene expression differences was novel and reduced intersubject heterogeneity of findings. We found gene expression differences related to miRNA-137 and other SZ-associated microRNAs, ELAVL1, BDNF, DISC-1, MECP2 and YWHAG associated findings, synapses, and receptors. Manual curation of our data may support transcription repression.
Highlights
Schizophrenia (SZ), a complex genetic disorder with no unifying conceptualization of the neuropathological or genetic correlates, is considered “a collection of neurodevelopmental disorders that involve alterations in brain circuits” [1,2,3,4]
Expressed Genes in the Anterior Nucleus (AN) of Schizophrenia Brains Compared with Normal Control Brains (AN SZ/normal controls (NC)) Fold Change 2.0, P < 0:05
We compared the transcriptome of accumulatively collected neurons from a disease-impacted SZ thalamic nucleus to a nondisease thalamic nucleus in the same subject and each nucleus in SZ vs. NC (S1, S2, S3, and S4)
Summary
Schizophrenia (SZ), a complex genetic disorder with no unifying conceptualization of the neuropathological or genetic correlates, is considered “a collection of neurodevelopmental disorders that involve alterations in brain circuits” [1,2,3,4]. It is a brain disorder with a heterogeneous symptom profile as well as multiple affected cellular correlates in particular thalamic and cortical circuits [5]. As pathology in one brain region can induce both structural and functional abnormalities in either mono- or polysynaptic pathways in other brain regions, we chose to study gene expression differences of a highly enriched neuronal population from a medial tier thalamic nucleus, the anterior (principal) nucleus (AN), that has previously been determined to be a SZ-associated region [5, 8]
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