The Role of Supraoptic Hypothalamic Arginine Vasopressin Neurons in Aging-Associated Water Balance and Thermoregulatory Deficits
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE310666 | GEO | 2026/05/28
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.
2010-11-29 | GSE25574 | GEO
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
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: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 Microarrays were interrogated with RNA extracted from the supraoptic nucleus of either euhydrated (n=5) or 7-days salt loaded (2% w/v; n=5) rats. Each microarray represented an independent pool of 5 animals, and for each condition, 5 microarrays were performed.
2015-02-05 | E-GEOD-65663 | biostudies-arrayexpress
Project description:Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) hibernate for several months each winter without access to water, but the mechanisms that maintain fluid homeostasis during hibernation are poorly understood. In torpor, when body temperature (TB) reaches 4°C, squirrels decrease metabolism, slow heart rate, and reduce plasma levels of the antidiuretic hormones arginine vasopressin (AVP) and oxytocin (OXT). Squirrels spontaneously undergo interbout arousal (IBA) every 2 weeks, temporarily recovering an active-like metabolism and a TB of 37°C for up to 48 h. Despite the low levels of AVP and OXT during torpor, profound increases in blood pressure and heart rate during the torpor-IBA transition are not associated with massive fluid loss, suggesting the existence of a mechanism that protects against diuresis at a low TB. Here, we demonstrate that the antidiuretic hormone release pathway is activated by hypothalamic supraoptic nucleus (SON) neurons early in the torpor-arousal transition. SON neuron activity, dense-core vesicle release from the posterior pituitary, and plasma hormone levels all begin to increase before TB reaches 10°C. In vivo fiber photometry of SON neurons from hibernating squirrels, together with RNA sequencing and c-FOS immunohistochemistry, confirms that SON is electrically, transcriptionally, and translationally active to monitor blood osmolality throughout the dynamic torpor-arousal transition. Our work emphasizes the importance of the antidiuretic pathway during the torpor-arousal transition and reveals that the neurophysiological mechanism that coordinates the hormonal response to retain fluid is active at an extremely low TB, which is prohibitive for these processes in non-hibernators.
2024-02-05 | GSE231418 | GEO
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: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:We describe age-related molecular and neuronal changes that disrupt mobility or energy balance based on brain region and genetic background. Compared to young mice, aged C57BL/6 mice exhibit marked locomotor (but not energy balance) impairments. In contrast, aged BALB mice exhibit marked energy balance (but not locomotor) impairments. Age-related changes in cerebellar or hypothalamic gene expression accompany these phenotypes. Aging evokes upregulation of immune pattern recognition receptors and cell adhesion molecules. However, these changes do not localize to microglia, the major CNS immunocyte. Consistent with a neuronal role, there is a marked age-related increase in excitatory synapses over the cerebellum and hypothalamus. Functional imaging of these regions is consistent with age-related synaptic impairments. These studies suggest that aging reactivates a developmental program employed during embryogenesis where immune molecules guide synapse formation and pruning. Renewed activity in this program may disrupt excitatory neurotransmission, causing significant behavioral deficits. keywords: aging, C57BL/6, BALB, CBA, hypothalamus, cerebellum, striatum, frontal cortex
2016-09-20 | GSE87102 | GEO
Project description:Arginine vasopressin (AVP) is a peptide hormone coded by the Avp gene, synthesized in the hypothalamus and secreted by the posterior pituitary. Dysregulation of AVP secretion contributes to a variety of human diseases. Previous studies of functional roles of AVP have been largely dependent on the use of Brattleboro rats, which manifest a spontaneous mutation in the Avp gene and lack circulating AVP. Despite their utility, Brattleboro rats are difficult to breed owing largely to the fixed nature of the Avp mutation, resulting in increased neonatal death and behavioral effects in the adults. Consequently, commercial breeders have ceased production, despite a continued need. Therefore, the main goal of this project is to create an effective experimental Avp knockout mouse model that could be used in renal and neuroendocrine research to study the control of water balance by AVP. We employed CRISPR/Cas9 to flox a portion of exon 2 of the Avp gene. Successful insertion of the two loxP sites was confirmed by PCR using primers flanking the targeted regions. Mice harboring the floxed allele were mated to B6.Cg-Tg(CAG-cre/Esr1*)5Amc/J mice that globally express a tamoxifen-inducible Cre recombinase. The resultant inducible Avp knockout mice (Cre+Avpflx/flx) show no signs of polydipsia or polyuria prior to induction, indicating that the floxed gene maintains its wild-type function. The administration of an exogenous inducer like tamoxifen to (8-10) week-old mice, induced Cre-mediated recombination that resulted in a decrease in urine osmolality from 2076 ± 138 to 122 ± 6 mOsm/kgH2O on day 31 after induction. Sanger sequencing demonstrated the expected 1245 bp deletion at the Avp locus. Immunoblotting of AQP2 in the inner medulla showed a significant decrease in AQP2 band density in (Cre+Avpflx/flx) mice to 27 ±1 4 % of values in Cre- floxed control mice. This inducible Avp knockout mouse model provides researchers with a valuable tool to investigate the consequences of Avp gene deletion in a controlled and inducible manner.
2025-08-05 | GSE304530 | 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