Showing papers by "Bruce R. Southey published in 2019"

Opioid-Induced Hyperalgesia Is Associated with Dysregulation of Circadian Rhythm and Adaptive Immune Pathways in the Mouse Trigeminal Ganglia and Nucleus Accumbens

Abstract: The benefits of opioid-based treatments to mitigate chronic pain can be hindered by the side effects of opioid-induced hyperalgesia (OIH) that can lead to higher consumption and risk of addiction. The present study advances the understanding of the molecular mechanisms associated with OIH by comparing mice presenting OIH symptoms in response to chronic morphine exposure (OIH treatment) relative to control mice (CON treatment). Using RNA-Seq profiles, gene networks were inferred in the trigeminal ganglia (TG), a central nervous system region associated with pain signaling, and in the nucleus accumbens (NAc), a region associated with reward dependency. The biological process of nucleic acid processing was over-represented among the 122 genes that exhibited a region-dependent treatment effect. Within the 187 genes that exhibited a region-independent treatment effect, circadian rhythm processes were enriched among the genes over-expressed in OIH relative to CON mice. This enrichment was supported by the differential expression of the period circadian clock 2 and 3 genes (Per2 and Per3). Transcriptional regulators in the PAR bZip family that are influenced by the circadian clock and that modulate neurotransmission associated with pain and drug addiction were also over-expressed in OIH relative to CON mice. Also notable was the under-expression in OIH relative to CON mice of the Toll-like receptor, nuclear factor-kappa beta, and interferon gamma genes and enrichment of the adaptive immune processes. The results from the present study offer insights to advance the effective use of opioids for pain management while minimizing hyperalgesia.

Seasonal adaptations of the hypothalamo-neurohypophyseal system of the dromedary camel

Abstract: The "ship" of the Arabian and North African deserts, the one-humped dromedary camel (Camelus dromedarius) has a remarkable capacity to survive in conditions of extreme heat without needing to drink water. One of the ways that this is achieved is through the actions of the antidiuretic hormone arginine vasopressin (AVP), which is made in a specialised part of the brain called the hypothalamo-neurohypophyseal system (HNS), but exerts its effects at the level of the kidney to provoke water conservation. Interestingly, our electron microscopy studies have shown that the ultrastructure of the dromedary HNS changes according to season, suggesting that in the arid conditions of summer the HNS is in an activated state, in preparation for the likely prospect of water deprivation. Based on our dromedary genome sequence, we have carried out an RNAseq analysis of the dromedary HNS in summer and winter. Amongst the 171 transcripts found to be significantly differentially regulated (>2 fold change, p value <0.05) there is a significant over-representation of neuropeptide encoding genes, including that encoding AVP, the expression of which appeared to increase in summer. Identification of neuropeptides in the HNS and analysis of neuropeptide profiles in extracts from individual camels using mass spectrometry indicates that overall AVP peptide levels decreased in the HNS during summer compared to winter, perhaps due to increased release during periods of dehydration in the dry season.

Jersey steer ruminal papillae histology and nutrigenomics with diet changes.

Abstract: The transition from a high forage to a high concentrate diet is an important milestone for beef cattle moving from a stocker system to the feedlot. However, little is known about how this transition affects the rumen epithelial gene expression. This study assessed the effects of the transition from a high forage to a high concentrate diet as well as the transition from a high concentrate to a high forage diet on a variety of genes as well as ruminal papillae morphology in rumen fistulated Jersey steers. Jersey steers (n = 5) were fed either a high forage diet (80% forage and 20% grain) and transitioned to a high concentrate diet (20% forage and 80% grain) or a high concentrate diet (40% forage and 60% grain) and transitioned to a high forage diet (100% forage). Papillae from the rumen were collected for histology and RT-qPCR analysis. Body weight had a tendency for significant difference (p = .08). Histological analysis did not show changes in papillae length or width in steers transitioning from a high forage to a high concentrate diet or vice versa (p > .05). Genes related to cell membrane structure (CLDN1, CLDN4, DSG1), fatty acid metabolism (CPT1A, ACADSB), glycolysis (PFKL), ketogenesis (HMGCL, HMGCS2, ACAT1), lactate/pyruvate (LDHA), oxidative stress (NQO1), tissue growth (AKT3, EGFR, EREG, IGFBP5, IRS1) and the urea cycle (SLC14A1) were considered in this study. Overall, genes related to fatty acid metabolism (ACADSB) and growth and development (AKT3 and IGFBP5) had a tendency for a treatment × day on trial interaction effect. These profiles may be indicators of rumen epithelial adaptations in response to changes in diet. In conclusion, these results indicate that changes in the composition of the diet can alter the expression of genes with specific functions in rumen epithelial metabolism.