Temporal dysregulation of cortical gene expression in the isolation-reared Wistar rat
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: David von Schack
PROVIDER: E-GEOD-19653 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The critical sequence of molecular, neurotransmission and synaptic disruptions that underpin the emergence of psychiatric disorders like schizophrenia remain to be established with progress only likely using animal models that capture key features of such disorders. Gene expression was assessed in social control and isolation reared rats at 4 increasing postnatal ages to relate gene expression dysregulation to behavioural and endophenotype emergence.
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Project description:To investigate the participation of deafness genes in the genetic program of the superior olivary complex (SOC), a prominent auditory brainstem center, we performed a comparative genome-wide microarray based gene expression analysis of the rat SOC and the rat brain at postnatal days (P) P4 and P25. Data were validated by qRT-PCR. Statistical analyses revealed 912 oligos up-regulated in the SOC at P4 and 1609 at P25. A total of 453 oligos were up-regulated in the SOC at both developmental stages. Subsequently, a list of 138 transcripts associated with hearing-impairment was extracted from publically available databases and literature. 26 of these transcripts were present in SOC-related gene signature lists, whereas only 11 were present in brain-related gene signature lists. Furthermore, in all 3 SOC-related gene signature lists, transcripts associated with hearing impairment were significantly enriched. Finally, there was a tendency of the SOC-related genes to map to human deafness loci with unknown etiology. Altogether, our study identified a tight genetic link between the SOC-related genetic program and deafness genes. The genome wide expression during the postnatal development of the SOC and the brain was investigated at two different time points: at postnatal (P) day 4 (before hearing onset) and at P25 (after hearing onset). Samples were hybridized onto two color platforms. At least 6 up to nine biological replicates per sample were performed.
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Project description:The superior olivary complex (SOC) is an essential auditory brainstem structure involved in sound localization. In order to identify the genetic program underlying its maturation, we profiled the transcriptome of the rat SOC at postnatal days (P)0, P4, P16, and P25, using genome-wide microarrays (41,012 sequences). Differences in gene expression between two consecutive stages were highest between P4 versus P16 (3.6%), but dropped to 0.06% between P16 versus P25. To identify SOC-related genetic programs, we also profiled the brain at P4 and P25. Differentially expressed sequences between SOC and brain almost doubled from P4 (4.4%) to P25 (7.6%). These datademonstrate considerable molecular specification around hearing onset, which is rapidly finalized. Prior to hearing onset, several transcription factors associated with the peripheral auditory system were up-regulated, likely coordinating auditory system development. Additionally, serotonin-related genes and crystalline-gamma subunits were highly expressed. The molecular repertoire of mature neurons was sculpted by SOC-related up- and down-regulation of several protein categories, among which voltage-gated channels and myelination were prominent. Comparison with the brain revealed a significant enrichment of deafness-related oligos in the SOC-related genetic program (26 in the SOC, only 11 in the brain). Furthermore, 29 out of 453 SOC-related oligos mapped within 19 genetic intervals associated with hearing impairment. Together, we identified sequential genetic programs in the SOC, thereby pinpointing candidates which may guide its development and ensure proper function. The enrichment of deafness-related genes in the SOC may have implications for restoring hearing, as central auditory structures might be more severely affected than previously appreciated. This SuperSeries is composed of the SubSeries listed below. The genome wide expression during the postnatal development of the SOC was investigated at four different time points: at postnatal (P) day 0, P4, P16 and P25. Concerning the brain, P4 and P25 were used. Samples were hybridized onto two color platforms. At least 6 up to nine biological replicates per sample were performed.
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