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.
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
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.
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.
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.
Project description:The cell bodies of hypothalamic magnocellular neurones (MCNs) are confined to the hypothalamic supraoptic nucleus (SON) whereas their axons project to the anatomically discrete posterior pituitary gland (PP). We have taken advantage of this unique anatomical structure to document proteome and phosphoproteome dynamics in neuronal cell bodies and axonal terminals in response to neuronal activation induced by water deprivation (WD). We have found that proteome and phosphoproteome responses to WD are very different between cell bodies and axonal terminals, indicating the need of each cell domain to differentially adapt in response to stimuli. Whilst changes in the proteome and phosphoproteome in the cell body are involved in protein synthesis and cytoskeleton reorganisation, respectively, in the axonal terminals they regulate synaptic vesicle cycle and secretion. Further, by comparison with transcriptome data, we have identified peptides that are not synthesised in the SON, but are present as a consequence of afferent delivery.
