Transcriptome and Methylome of the Supraoptic Nucleus Provides Insights into the Age-dependent Loss of Neuronal Plasticity
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PROVIDER: PRJNA967010 | ENA |
REPOSITORIES: ENA
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Project description:The age-dependent loss of neuronal plasticity is a well-known phenomenon that is poorly understood. The loss of this capacity for axonal regeneration is emphasized following traumatic brain injury, which is a major cause of disability and death among adults in the US. We have previously shown the intrinsic capacity of magnocellular neurons within the supraoptic nucleus to undergo axonal regeneration following unilateral axotomization in an age-dependent manner. The aim of this research was to determine the age-dependent molecular mechanisms that may underlie this phenomenon. As such, we characterized the transcriptome and DNA methylome of the supraoptic nucleus in uninjured 35-day old rats and 125-day old rats. Our data indicates the downregulation of a large number of axonogenesis related transcripts in 125-day old rats compared to 35-day old rats. Specifically, several semaphorin and ephrin genes were downregulated, as well as growth factors including FGF's, insulin-like growth factors (IGFs), and brain-derived neurotrophic factor (BDNF). Differential methylation analysis indicates enrichment of biological processes involved in axonogenesis and axon guidance. Conversely, we observed a robust and specific upregulation of MHCI related transcripts. This may involve the activator protein 1 (AP-1) transcription factor complex as motif analysis of differentially methylated regions indicate enrichment of AP-1 binding sites in hypomethylated regions. Together, our data suggests a loss of pro-regenerative capabilities with age which would prevent axonal growth and appropriate innervation following injury.
| S-EPMC10498476 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-08-16 | GSE231617 | 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:Our prior studies indicat age-dependent contralateral axonal sprouting following unilateral lesion of magnocellular neurons in the supraoptic nucleus. We performed Oxford Nanopore sequencing of the rat supraoptic nucleus to determine changes in DNA methylation with age.
2023-08-16 | GSE231615 | GEO
Project description:Our prior studies indicat age-dependent contralateral axonal sprouting following unilateral lesion of magnocellular neurons in the supraoptic nucleus. To understand the changes in the transcriptome that underlies this phenomenon, we performed RNA-seq and functional analysis of the rat supraoptic nucleus to determine changes in gene expression with age.
2023-08-16 | GSE231616 | 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. Keywords: dehydrated, SON, clone
2005-12-02 | GSE3132 | 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 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: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 hypothalamic supraoptic nucleus (SON) is a core osmoregulatory control centre that deciphers information about the metabolic state of the organism and orchestrates appropriate homeostatic (endocrine) and allostatic (behavioural) responses. We have used RNA sequencing to describe the polyadenylated transcriptome of the SON of the male Wistar Han rat. These data have been mined to generate comprehensive catalogues of functional classes of genes (enzymes, transcription factors, endogenous peptides, G protein coupled receptors, transporters, catalytic receptors, channels and other pharmacological targets) expressed in this nucleus in the euhydrated state, and that together form the basal substrate for its physiological interactions. We have gone on to show that fluid deprivation for 3 days (dehydration) results in changes in the expression levels of 2247 RNA transcripts, which have similarly been functionally catalogued, and further mined to describe enriched gene categories and putative regulatory networks (Regulons) that may have physiological importance in SON function related plasticity.
2021-05-25 | GSE175461 | 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