Temporal dysregulation of cortical gene expression in the isolation-reared Wistar rat
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ABSTRACT: 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. We prepared cDNA from brain tissue samples of the medial prefrontal cortex from socially reared Wistar rats (Soc) and matching isolation reared cohorts (Iso) at postnatal day (P) 30, 40, 60 and 80.
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.
Project description:To study the effect of sensory experience on 3D genome structure of the mouse brain, we performed Dip-C on 1,692 single cells from the visual cortex of dark-reared and control mice at different ages throughout the first postnatal month.
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.
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.
Project description:While multifactorial in origin, one of the most prevalent and impactful consequences of social isolation is an increase in cancer mortality. Using a preclinical model in Sprague Dawley rats, we found that social isolation increased the risk of mammary tumor recurrence after completion of antiestrogen therapy. The increased recurrence risk was associated with an upregulation of IL6/JAK/STAT3 signaling in the mammary glands and tumors and suppression of mitochondrial oxidative phosphorylation (OXPHOS) pathway. Also inhibited were genes involved in mitochondrial pyruvate transport and the conversion of pyruvate to acetyl CoA but lactate levels were not altered. In addition, social isolation increased the expression of receptor for advanced glycation end-products (RAGE), consistent with the impaired insulin sensitivity and weight gain linked to social isolation. All these changes are commonly associated with aging. In socially isolated animals consumption of the anti-inflammatory 12 herb mixture Jaeumganghwa-tang (JGT) inhibited IL6/JAK/STAT3 signaling, upregulated OXPHOS signaling, suppressed expression of the RAGE ligands S100a8 and S100a9, and prevented the increased risk of mammary cancer recurrence. In summary, increased breast cancer mortality among socially isolated survivors may be most effectively prevented by focusing on the period following the completion of endocrine therapy using tools that inhibit IL6/JAK/STAT3 inflammatory cytokine signaling and reverse disrupted OXPHOS.
Project description:The superior olivary complex (SOC) is a prominent auditory brainstem center and represents one of the prime model systems to study the development of sensory circuits. We recently performed genome-wide microarray studies to analyze the SOC-related genetic program at postnatal day (P)4 and P25. Here, we extended this analysis by including two additional time points, P0 and P16. Data sets were validated by qRT-PCR. Statistical analysis were performed for the different developmental time points as well as with for differences between the SOC and our previously analyzed brain samples. This analysis revealed that after hearing-onset (P16 and P25), 918 oligos were up-regulated and 810 oligos down-regulated in the SOC compared to the two prehearing stages (P0 and P4). Of the up-regulated oligos, 530 were significantly higher expressed compared to the brain at P25. Concerning neurotransmission, SOC-related elevation was mainly observed for K+ channels, G-proteins, and myelination-related proteins, whereas Ca2+-related proteins showed a decreased expression. In the pre-hearing period, 47 oligos were up-regulated compared to the brain. Several of them were transcription factors, previously associated with other auditory structures, and might ensure coordinated development of peripheral and central auditory structures. Stage-specific comparison identified distinct genetic programs during development: Circuit formation/refinement at P4; myelination and circuit refinement/consolidation at P16; and neuroprotection at P25. Altogether, our study defines the genetic program of postnatal SOC development and provides strong functional candidates for various developmental processes. The genome wide expression during the postnatal development of the SOC was investigated at two different time points: at postnatal (P) day 0 (before hearing onset) and P16 (after hearing onset). Samples were hybridized onto two color platforms. At least 6 up to nine biological replicates per sample were performed.
Project description:Larvae were reared on standard diet until early third instar, at which time they were washed and transferred to standard diet lacking yeast. The animals remained on this diet until four days after emergence, when one group of adults was switched back to standard diet containing yeast (group Y) while another remained on the diet lacking yeast (group NY). Flies from both groups were killed every hour for the next twelve hours, creating 24 samples across the two treatments. In addition, four samples of flies were killed just before the start of the time course and used as baseline replicates for the no yeast (NY) and yeast (Y) treatments. Baseline replicates were temporally ordered as noted for change-point analysis. No yeast (NY) treatment samples at hours four and eight did not yield microarray data due to insufficient RNA.
Project description:Background: Aquaculture of the black tiger prawn Penaeus monodon remains severely constrained by an almost total dependence on wild-caught broodstock. Reliance on wild-caught broodstock stems, for the most part, from reduced reproductive potential of captive-reared females. Reproductive performance of captive-reared females is usually characterised by longer latency period, lower egg production, egg hatch rates and post-larval survivorship compared with their wild-caught counterparts. Improved understanding of the cellular and associated molecular events occurring during peneaid ovarian maturation could therefore be fundamental to improving reproductive success of captive-reared animals. Methodology/Principle Findings: In support of other studies, our histological analyses of developing oocytes revealed differences between wild-caught and captive-reared P. monodon, including reduced lipid accumulation in oocytes of captive-reared animals. We have employed oligonucleotide microarray analysis to compare expression profiles of genes involved in ovarian maturation among wild-caught and captive-reared animals. Custom oligonucleotide microarrays were constructed and screened with transcripts derived from the ovary, cephalothorax and eyestalk from animals of all ovarian maturation stages. Ovarian maturation-related differential expression patterns were observed for 111 transcripts, with 53 transcripts displaying differential expression between wild-caught and captive-reared animals. Notably transcripts encoding vitellogenin - the major egg yolk protein precursor, and a lipid storage droplet protein (which we named pmLSD) which is involved in lipid accumulation, were found to be more highly expressed in wild-caught animals. pmLSD transcripts localise to pre-vitellogenic oocytes of wild-caught animals and the pmLSD protein is exclusively localised to the surface of lipid droplets of oocytes at vitellogenic and cortical rod stages.