Hypothalamic transcriptome plasticity in two rodent species reveals divergent differential gene expression but conserved pathways
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ABSTRACT:
ORGANISM(S): Mus musculus Rattus norvegicus
PROVIDER: GSE25574 | GEO | 2010/11/29
SECONDARY ACCESSION(S): PRJNA133885
REPOSITORIES: GEO
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Project description:We have addressed the question of how different rodent species cope with the life-threatening homeostatic challenge of dehydration at the level of transcriptome modulation in the supraoptic nucleus (SON), a specialised hypothalamic neurosecretory apparatus responsible for the production of the antidiuretic peptide hormone arginine vasopressin (AVP). AVP maintains water balance by promoting water conservation at the level of the kidney. Dehydration evokes a massive increase in the regulated release of AVP from SON axon terminals located in the posterior pituitary, and this is accompanied by a plethora of changes in the morphology, electrophysiological properties, biosynthetic and secretory activity of this structure. Microarray analysis was used to generate a definitive catalogue of the genes expressed in the mouse SON, and to describe how the gene expression profile changes in response to dehydration. Comparison of the genes differentially expressed in the mouse SON as a consequence of dehydration with those of the rat has revealed many similarities, pointing to common processes underlying the function-related plasticity in this nucleus. In addition we have identified many genes that are differentially expressed in a species-specific manner. However, in many cases, we have found that the hyperosmotic cue can induce species-specific alterations in the expression of different genes in the same pathway. The same functional end can be served by different means, via differential modulation, in different species, of different molecules in the same pathway. We suggest that pathways, rather than specific genes, should be the focus of integrative physiological studies based on transcriptome data. Animals. Adult male C57BL/6 mice (Harlan Sera-Lab, Loughborough, UK) were group housed (4 per cage) under controlled temperature (21+ 2ºC) and diurnal light conditions (14-h light, 10-h dark, lights on at 05.00). Food and water were available ad libitum until the experiment commenced. Complete fluid deprivation was imposed for 48 hours starting at 11.00 a.m. Control animals maintained free access to drinking water, and both groups had access to standard laboratory rodent chow. Experiments on adult male rats described previously (27). All procedures were conducted in strict accordance with the Animal Scientific Procedures Act (1986), UK, and were approved by the local University of Bristol Ethical Review Process. Tissue collection. Mice were killed using cervical dislocation and the brain was carefully removed from the cranium and snap frozen using powdered dry ice and stored at -80oC for no more than 14 days. Sections of brain (14μm) were cut using an RNase free cryostat and mounted onto RNase free membrane coated glass slides (P.A.L.M. Membrane slides; P.A.L.M. Microlaser Technologies). Immediately after sectioning, frozen sections were thawed and fixed (30s; in 95% [v/v] EtOH), rehydrated (30s in each of 75% [v/v] and 50% [v/v] EtOH) before being stained (60s 1% [v/v] cresyl violet). Sections were then dehydrated in a graded EtOH series (30s in each of 50% [v/v], 75% [v/v] and 95% [v/v]. then 2x 30s in 100% [v/v]). Laser microdissection was performed using a P.A.L.M. MicrolaserSystem (P.A.L.M. Microlaser Technologies). The SON was identified with reference to Franklin and Paxinos (28) and the tissue from each animal was independently pooled into collection vials containing RNAlater® (Ambion, Huntingdon, UK). A single operative carried out all dissections. Total RNA was isolated without delay (within 24h) according to standard procedures that accompany the Ambion RNAqueous MicroKit (Ambion). Microarray analysis. Separate microarrays (n=4) were probed using independently generated target. For each completely independent replicate, tissue from 1 mouse was used for RNA extraction.
2010-11-29 | E-GEOD-25574 | biostudies-arrayexpress
Project description:The magnocellullar neurons (MCNs) of the supraoptic nucleus (SON) of the hypothalamus are the principle source of the neuropeptide hormone vasopressin (VP), which has a crucial role in osmoregulation. Physiological activation of the SON by dehydration results is a massive release of VP from stores in posterior pituitary axon terminals into the general circulation. By binding to V2-type receptors located in the kidney, VP decrease the amount of water lost in urine. Osmotic activation of the SON is accompanied by a dramatic morphological and functional remodelling. We have sought to understand the mechanistic basis of this plasticity in terms of the differential expression of genes. To identify such genes, we adopted a completely unbiased and global approach based on Suppressive Subtractive Hybridisation-Polymerase Chain Reaction (SSH-PCR) Using this method, we generated a library of clones putatively differentially expressed in control vs dehydrated SON. In order to rapidly screen this library, 1152 of these clones were subjected to microarray analysis, resulting in the identification of 459 differentially expressed clones, 56 of which were sequenced. Many of these clones are expressed sequences that are new to science. Four of these were shown by in situ hybridisation (ISH) to be significantly up- or down-regulated in the SON following dehydration. These genes may represent novel effectors or mediators of SON physiological remodelling. Keywords: dehydrated, SON, clone
2005-12-02 | GSE3132 | GEO
Project description:The magnocellullar neurons (MCNs) of the supraoptic nucleus (SON) of the hypothalamus are the principle source of the neuropeptide hormone vasopressin (VP), which has a crucial role in osmoregulation. Physiological activation of the SON by dehydration results is a massive release of VP from stores in posterior pituitary axon terminals into the general circulation. By binding to V2-type receptors located in the kidney, VP decrease the amount of water lost in urine. Osmotic activation of the SON is accompanied by a dramatic morphological and functional remodelling. We have sought to understand the mechanistic basis of this plasticity in terms of the differential expression of genes. To identify such genes, we adopted a completely unbiased and global approach based on Suppressive Subtractive Hybridisation-Polymerase Chain Reaction (SSH-PCR) Using this method, we generated a library of clones putatively differentially expressed in control vs dehydrated SON. In order to rapidly screen this library, 1152 of these clones were subjected to microarray analysis, resulting in the identification of 459 differentially expressed clones, 56 of which were sequenced. Many of these clones are expressed sequences that are new to science. Four of these were shown by in situ hybridisation (ISH) to be significantly up- or down-regulated in the SON following dehydration. These genes may represent novel effectors or mediators of SON physiological remodelling. 4 chips were hybridised with control SON and compared to 4 chips hybridised with dehydrated SON
2010-06-30 | E-GEOD-3132 | biostudies-arrayexpress
Project description:The hypothalamo-neurohypophyseal system (HNS) is crucial for osmoregulation. The HNS consists of the magnocellular neurons (MCNs) of the hypothalamus that have their axons terminating in the posterior pituitary. The HNS exerts its role in water balance via the release of the anti-diuretic hormone vasopressin (VP). Following dehydration VP is released into the general circulation. By binding to V2-type receptors located in the kidney, VP decrease the amount of water lost in urine. An osmotic stimulus also elicits an increase in VP gene expression and a functional remodelling of the entire HNS. We want to understand this plasticity in terms of the co-ordinated reprogramming of gene expression. We thus used Affymetrix U34a rat GeneChips to examine the dynamics of gene expression plasticity over the duration of a dehydration stimulus. Arrays were probed in triplicate with targets derived from SON of control rats, and rats dehydrated for 1 and for 3 days. Transcripts were thus identified that respond early to dehydration (up- or down-regulated after only 1day of dehydration), or that respond late (up- or down-regulated at 3 days of dehydration). Experiment Overall Design: 3 chips hybridised with control SON were compared to 3 chips hybridised with 1 day dehydrated SON and 3 chips hybridised with 3 day dehydrated SON
2007-11-06 | E-GEOD-3131 | biostudies-arrayexpress
Project description:The magnocellular neurons (MCNs) of the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus are the principal site of biosynthesis of prepropeptide precursor of the antidiuretic hormone vasopressin (VP). This precursor is processed during anterograde axonal transportation to terminals in the posterior pituitary gland, where biologically active VP is stored until released into the general circulation in response to physiological activation of the SON by osmotic cues. By binding to V2-type receptors located in the kidney, VP decreases the amount of water lost in urine. Osmotic activation of the SON is accompanied by a dramatic morphological and functional remodelling. We have sought to understand the mechanistic basis of this plasticity in terms of the differential expression of genes. To identify such genes, we adopted an unbiased global approach based on Suppressive Subtractive Hybridisation-Polymerase Chain Reaction (SSH-PCR) Using this method, we generated libraries of clones putatively differentially expressed in control vs dehydrated SON. In order to rapidly screen these libraries, 1152 clones were subjected to microarray analysis, resulting in the identification of 459 differentially expressed transcripts. cDNA clones corresponding 56 of these RNAs were sequenced, revealing many of them to be novel ESTs. Four transcripts were shown by in situ hybridisation (ISH) to be significantly up- or down-regulated in the SON following dehydration. These genes may represent novel effectors or mediators of SON physiological remodelling. Keywords: dehydration, SON, NIA
2005-12-02 | GSE3133 | GEO
Project description:The supraoptic nucleus (SON) of the hypothalamus is an important integrative brain structure that co-ordinates responses to perturbations in water balance and regulates maternal physiology through the release of the neuropeptide hormones vasopressin and oxytocin into the circulation. Both dehydration and lactation evoke a dramatic morphological remodelling of the SON, a process known as function-related plasticity. We hypothesise that some of the changes seen in SON remodelling are mediated by differential gene expression, and have thus used microarrays to document global changes in transcript abundance that accompany chronic dehydration in female rats, and in lactation. In situ hydridisation analysis has confirmed the differential expression of 3 of these genes, namely Tumour necrosis factor induced protein 6, Gonadotrophin inducible transcription factor 1 and Ornithine decarboxylase antizyme inhibitor 1. Comparison of differential gene expression patterns in male and female rats subjected to dehydration and in lactating rats has enabled the identification of common elements that are significantly enriched in gene classes with particular functions. Two of these are related to the requirement for increased protein synthesis and hormone delivery in the physiologically stimulated SON (translation initiation factor activity and endoplasmic reticulum-Golgi intermediate compartment respectively), whilst others are consistent with concept of SON morphological plasticity (collagen fibril organisation, extracellular matrix organization and biogenesis, extracellular structure organization and biogenesis and homophilic cell adhesion). We suggest that the genes co-ordinately regulated in the SON as a consequence of dehydration and lactation form a network that mediates the plastic processes operational in the physiologically activated SON.
2011-12-29 | GSE30733 | GEO
Project description:The supraoptic nucleus (SON) of the hypothalamus is an important integrative brain structure that co-ordinates responses to perturbations in water balance and regulates maternal physiology through the release of the neuropeptide hormones vasopressin and oxytocin into the circulation. Both dehydration and lactation evoke a dramatic morphological remodelling of the SON, a process known as function-related plasticity. We hypothesise that some of the changes seen in SON remodelling are mediated by differential gene expression, and have thus used microarrays to document global changes in transcript abundance that accompany chronic dehydration in female rats, and in lactation. In situ hydridisation analysis has confirmed the differential expression of 3 of these genes, namely Tumour necrosis factor induced protein 6, Gonadotrophin inducible transcription factor 1 and Ornithine decarboxylase antizyme inhibitor 1. Comparison of differential gene expression patterns in male and female rats subjected to dehydration and in lactating rats has enabled the identification of common elements that are significantly enriched in gene classes with particular functions. Two of these are related to the requirement for increased protein synthesis and hormone delivery in the physiologically stimulated SON (translation initiation factor activity and endoplasmic reticulum-Golgi intermediate compartment respectively), whilst others are consistent with concept of SON morphological plasticity (collagen fibril organisation, extracellular matrix organization and biogenesis, extracellular structure organization and biogenesis and homophilic cell adhesion). We suggest that the genes co-ordinately regulated in the SON as a consequence of dehydration and lactation form a network that mediates the plastic processes operational in the physiologically activated SON. Each independent microarray sample represented the SON from either 5 female euhydrated, 5 dehydrated (water restriction for 72hours with food ad libitum) or 11 days lactating. In total, 5 microarrays were performed for the Dehydrated and the Lactation groups and 4 for the euhydrated controls. Samples within each group may be considered to be both biological and technical replicates. The GeneSpring-derived MAS5 data described in the publication is not included in this submission.
2011-12-29 | E-GEOD-30733 | biostudies-arrayexpress
Project description:The hypothalamo-neurohypophyseal system (HNS) is crucial for osmoregulation. The HNS consists of the magnocellular neurons (MCNs) of the hypothalamus that have their axons terminating in the posterior pituitary. The HNS exerts its role in water balance via the release of the anti-diuretic hormone vasopressin (VP). Following dehydration VP is released into the general circulation. By binding to V2-type receptors located in the kidney, VP decrease the amount of water lost in urine. An osmotic stimulus also elicits an increase in VP gene expression and a functional remodelling of the entire HNS. We want to understand this plasticity in terms of the co-ordinated reprogramming of gene expression. We thus used Affymetrix U34a rat GeneChips to examine the dynamics of gene expression plasticity over the duration of a dehydration stimulus. Arrays were probed in triplicate with targets derived from SON of control rats, and rats dehydrated for 1 and for 3 days. Transcripts were thus identified that respond early to dehydration (up- or down-regulated after only 1day of dehydration), or that respond late (up- or down-regulated at 3 days of dehydration). Keywords: SON, Dehydration, clone
2006-08-15 | GSE3131 | GEO
Project description:The magnocellular neurons (MCNs) of the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus are the principal site of biosynthesis of prepropeptide precursor of the antidiuretic hormone vasopressin (VP). This precursor is processed during anterograde axonal transportation to terminals in the posterior pituitary gland, where biologically active VP is stored until released into the general circulation in response to physiological activation of the SON by osmotic cues. By binding to V2-type receptors located in the kidney, VP decreases the amount of water lost in urine. Osmotic activation of the SON is accompanied by a dramatic morphological and functional remodelling. We have sought to understand the mechanistic basis of this plasticity in terms of the differential expression of genes. To identify such genes, we adopted an unbiased global approach based on Suppressive Subtractive Hybridisation-Polymerase Chain Reaction (SSH-PCR) Using this method, we generated libraries of clones putatively differentially expressed in control vs dehydrated SON. In order to rapidly screen these libraries, 1152 clones were subjected to microarray analysis, resulting in the identification of 459 differentially expressed transcripts. cDNA clones corresponding 56 of these RNAs were sequenced, revealing many of them to be novel ESTs. Four transcripts were shown by in situ hybridisation (ISH) to be significantly up- or down-regulated in the SON following dehydration. These genes may represent novel effectors or mediators of SON physiological remodelling. 3 chips were hybridised with control SON and compared to 3 chips hybridised with dehydrated SON
2010-06-30 | E-GEOD-3133 | biostudies-arrayexpress
Project description:Salt loading (SL) and water deprivation (WD) are experimental challenges that are often used to study the osmotic circuitry of the brain. Central to this circuit is the supraoptic nucleus (SON) of the hypothalamus, which is responsible for the biosynthesis of the hormones, vasopressin (AVP) and oxytocin (OXT), and their transport to terminals that reside in the posterior lobe of the pituitary. Upon osmotic challenge evoked by a change in blood volume or osmolality, the SON undergoes a function related plasticity that creates an environment that allows for an appropriate hormone response. Here, we have described the impact of SL and WD compared to euhydrated (EU) controls in terms of drinking and eating behaviour, body weight and recorded physiological data including circulating hormone data and plasma and urine osmolality. We have also used microarrays to profile the transcriptome of the SON following SL
2015-02-05 | GSE65663 | GEO