Whole transcriptome organisation in the dehydrated supraoptic nucleus

Abstract

The supraoptic nucleus (SON) is part of the central osmotic circuitry that synthesises the hormone vasopressin (Avp) and transports it to terminals in the posterior lobe of the pituitary. Following osmotic stress such as dehydration, this tissue undergoes morphological, electrical and transcriptional changes to facilitate the appropriate regulation and release of Avp into the circulation where it conserves water at the level of the kidney. Here, the organisation of the whole transcriptome following dehydration is modelled to fit Zipf's law, a natural power law that holds true for all natural languages, that states if the frequency of word usage is plotted against its rank, then the log linear regression of this is -1. We have applied this model to our previously published euhydrated and dehydrated SON data to observe this trend and how it changes following dehydration. In accordance with other studies, our whole transcriptome data fit well with this model in the euhydrated SON microarrays, but interestingly, fit better in the dehydrated arrays. This trend was observed in a subset of differentially regulated genes and also following network reconstruction using a third-party database that mines public data. We make use of language as a metaphor that helps us philosophise about the role of the whole transcriptome in providing a suitable environment for the delivery of Avp following a survival threat like dehydration.

A comparison of physiological and transcriptome responses to water deprivation and salt loading in the rat supraoptic nucleus

“…We have observed in previous work that WD regulates fewer transcripts than does other stimuli in the same tissue, for example, food restriction (22,25), and that the transcriptome of the SON becomes more organized after a survival threat. When the transcriptome response to WD is modelled, the emerging distribution is different from that found in the EU transcriptome, a trend we have previously placed within the context of enhanced transcriptome organization (24). Because a different physiological response must be mounted to different survival threats, global transcriptome responses to either WD or SL in the SON may also be different.…”

“…These morphological changes are accompanied by biochemical events such as a strong activation of the cAMP pathway (10) and transcriptional events that extend beyond simple AVP and OXT biogenesis (32,46). We have previously shown that WD in both male and female rats is capable of modulating gene expression in the SON (23,45) and that this modulation is a global transcriptome response (24). We have also recently demonstrated that many of the genes that are regulated in the SON in response to WD are also altered by lactation (45).…”

Unsupervised Network Analysis of the Plastic Supraoptic Nucleus Transcriptome Predicts Caprin2 Regulatory Interactions

“…NCBI Accession numbers (incorporating controls): male dehydration, GSE3110; male salt loading, GSE65663; female dehydration and lactation, GSE30733. We note that the biological importance of salt and water balance, especially after challenge, ensures small standard deviations (10%) in the data (Hindmarch et al, 2013). Validation using quantitative reverse transcription PCR (qRT-PCR; Hindmarch et al, 2006; Qiu et al, 2011; Greenwood et al, 2015; Fig.…”

“…In addition, It has been demonstrated that the AVP mRNAs is subject to post-transcriptional modification in the form of an increase in the length of the 3’ poly(A) tail following dehydration (Carrazana et al, 1988; Zingg et al, 1988; Carter and Murphy, 1989; Murphy and Carter, 1990). Recently, microarrays have been used to document transcriptome-wide changes in gene expression in the SON of male rats subject to salt-loading and dehydration (Hindmarch et al, 2006; Greenwood et al, 2015), and in female rats in response to both dehydration and 11 d of lactation (Qiu et al, 2011), and it has been suggested that these changes are part of an organized response to maintaining homeostasis in a changing environment (Hindmarch et al, 2013). …”

Mapping Molecular Datasets Back to the Brain Regions They are Extracted from: Remembering the Native Countries of Hypothalamic Expatriates and Refugees

“…Dehydration/salt-loading can alter the HNS transcriptome, with certain genes enriched in the PVH and SO being especially sensitive to this physiological condition [142, 167, 354, 412]; also see [170]). Similarly, the HNS proteome is also altered by dehydration, where 25 and 45 proteins have been reported to be affected in the SO and neurointermediate lobe (NIL), respectively [138].…”