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

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, arginine vasopressin (AVP) and oxytocin (OXT), and their transport to terminals that reside in the posterior lobe of the pituitary. On 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 with euhydrated (EU) controls in terms of drinking and eating behavior, 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 and remined data from the SON that describes the transcriptome response to WD. From a list of 2,783 commonly regulated transcripts, we selected 20 genes for validation by qPCR. All of the 9 genes that have already been described as expressed or regulated in the SON by osmotic stimuli were confirmed in our models. Of the 11 novel genes, 5 were successfully validated while 6 were false discoveries.

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Characterization of the major brain osmolytes that accumulate in salt-loaded rats

AJP Renal Physiology ◽

10.1152/ajprenal.1989.257.6.f1108 ◽

1989 ◽

Vol 257 (6) ◽

pp. F1108-F1116 ◽

Cited By ~ 10

Author(s):

C. W. Heilig ◽

M. E. Stromski ◽

J. D. Blumenfeld ◽

J. P. Lee ◽

S. R. Gullans

Keyword(s):

Amino Acids ◽

Water Deprivation ◽

Sodium Concentration ◽

Plasma Sodium ◽

Organic Solutes ◽

Salt Loading ◽

Biochemical Assays ◽

Plasma Sodium Concentration ◽

1H Nuclear Magnetic Resonance ◽

The Brain

Previous studies demonstrated an accumulation of “idiogenic osmoles” in the brain with chronic salt loading. Amino acids are known to constitute a portion of these solutes, but the balance of the solutes has yet to be fully characterized. In the present study, 1H-nuclear magnetic resonance (NMR) spectroscopy and biochemical assays of rat brain were used to identify and quantify changes in organic solutes in two different animal models of hypernatremia: hypertonic salt loading and water deprivation. Five days of salt loading increased plasma sodium concentration (PNa) to 165 meq/l and 3 days of water deprivation increased PNa to 151 meq/l, compared with 141 meq/l in controls. Amino acids, methylamines, and polyols were all significantly higher in salt-loaded animals compared with controls. Specifically, higher contents of glutamine (+65%), glutamate (+27%), myo-inositol (+36%), phosphocreatine + creatine (PCr + Cr) (32%), glycerophosphorylcholine (GPC) (+75%), and choline (+114%) were observed. Sorbitol and betaine, osmolytes known to accumulate in the hypertonic inner medulla, were present in low amounts in the brain and were unchanged with salt loading. In contrast to the results with salt loading, no accumulation of brain organic solutes was detected after 3 days of water deprivation. Based on these findings, we propose that amino acids, methylamines, and polyols function as osmoregulatory solutes in the brains of salt-loaded rats in a manner similar to that observed in other biological systems, whereas 3 days of water deprivation is an insufficient stimulus for their accumulation.

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Molecular Characterization and Biological Function of Neuroendocrine Regulatory Peptide-3 in the Rat

Endocrinology ◽

10.1210/en.2011-1539 ◽

2012 ◽

Vol 153 (3) ◽

pp. 1377-1386 ◽

Cited By ~ 13

Author(s):

Hiroaki Fujihara ◽

Kazuki Sasaki ◽

Emi Mishiro-Sato ◽

Toyoaki Ohbuchi ◽

Govindan Dayanithi ◽

...

Keyword(s):

Paraventricular Nucleus ◽

Supraoptic Nucleus ◽

Biologically Active ◽

Regulatory Peptide ◽

Salt Loading ◽

Peptidomic Analysis ◽

Biologically Active Peptide ◽

Body Fluid Balance ◽

The Brain

Neuroendocrine regulatory peptide (NERP)-3, derived from the neurosecretory protein VGF (non-aconymic), is a new biologically active peptide identified through peptidomic analysis of the peptides secreted by an endocrine cell line. Using a specific antibody recognizing the C-terminal region of NERP-3, immunoreactive (ir)-NERP-3 was identified in acid extracts of rat brain and gut as a 30-residue NERP-3 with N-terminal pyroglutamylation. Assessed by radioimmunoassay, ir-NERP-3 was more abundant in the brain, including the posterior pituitary (PP), than in the gut. Immunohistochemistry demonstrated that ir-NERP-3 was significantly increased in the suprachiasmatic nucleus, the magnocellular division of the paraventricular nucleus, and the external layer of the median eminence, but not in the supraoptic nucleus, after dehydration. The immunoreactivity was, however, markedly decreased in all of these locations after chronic salt loading. Intracerebroventricular administration of NERP-3 in conscious rats induced Fos expression in a subset of arginine vasopressin (AVP)-containing neurons in the supraoptic nucleus and the magnocellular division of the paraventricular nucleus. On in vitro isolated rat PP preparations, NERP-3 caused a significant AVP release in a dose-related manner, suggesting that NERP-3 in the PP could be an autocrine activator of AVP release. Taken together, the present results suggest that NERP-3 in the hypothalamo-neurohypophyseal system may be involved in the regulation of body fluid balance.

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Genetic deletion of connexin 37 causes polyuria and polydipsia

PLoS ONE ◽

10.1371/journal.pone.0244251 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0244251

Author(s):

Jianxiang Xue ◽

Linto Thomas ◽

Jessica A. Dominguez Rieg ◽

Robert A. Fenton ◽

Timo Rieg

Keyword(s):

Water Deprivation ◽

Fluid Intake ◽

Collecting Duct ◽

Urine Osmolality ◽

Physiological Data ◽

Thick Ascending Limb ◽

Renal Vasculature ◽

Paracrine Factors ◽

Water Handling ◽

Connexin 37

The connexin 37 (Cx37) channel is clustered at gap junctions between cells in the renal vasculature or the renal tubule where it is abundant in basolateral cell interdigitations and infoldings of epithelial cells in the proximal tubule, thick ascending limb, distal convoluted tubule and collecting duct; however, physiological data regarding its role are limited. In this study, we investigated the role of Cx37 in fluid homeostasis using mice with a global deletion of Cx37 (Cx37-/- mice). Under baseline conditions, Cx37-/- had ~40% higher fluid intake associated with ~40% lower urine osmolality compared to wild-type (WT) mice. No differences were observed between genotypes in urinary adenosine triphosphate or prostaglandin E2, paracrine factors that alter renal water handling. After 18-hours of water deprivation, plasma aldosterone and urine osmolality increased significantly in Cx37-/- and WT mice; however, the latter remained ~375 mmol/kg lower in Cx37-/- mice, an effect associated with a more pronounced body weight loss despite higher urinary AVP/creatinine ratios compared to WT mice. Consistent with this, fluid intake in the first 3 hours after water deprivation was 37% greater in Cx37-/- vs WT mice. Cx37-/- mice showed significantly lower renal AQP2 abundance and AQP2 phosphorylation at serine 256 than WT mice in response to vehicle or dDAVP, suggesting a partial contribution of the kidney to the lower urine osmolality. The abundance and responses of the vasopressin V2 receptor, AQP3, NHE3, NKCC2, NCC, H+-ATPase, αENaC, γENaC or Na+/K+-ATPase were not significantly different between genotypes. In summary, these results demonstrate that Cx37 is important for body water handling.

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EFFECT OF SALT-LOADING, THIRST AND WATER-LOADING ON TRANSPORT AND TURNOVER OF NEUROHYPOPHYSIAL PROTEINS OF THE RAT

Journal of Endocrinology ◽

10.1677/joe.0.0520087 ◽

1972 ◽

Vol 52 (1) ◽

pp. 87-105 ◽

Cited By ~ 30

Author(s):

A. NORSTRÖM ◽

J. SJÖSTRAND

Keyword(s):

Axonal Transport ◽

Supraoptic Nucleus ◽

Slow Phase ◽

Nacl Solution ◽

Time Intervals ◽

Neural Lobe ◽

Salt Loading ◽

Water Loading ◽

Short Time ◽

Osmotic Stimuli

SUMMARY The effect of salt-loading, thirst and water-loading on the axonal transport and turnover of neurohypophysial proteins in rats was investigated by measuring the radioactivity of the neural lobe proteins at various time intervals after injection of [35S]cysteine into the region of the supraoptic nucleus. Osmotic stimuli did not markedly affect the rate of transport of either the rapid or the slow phase of axonal transport of proteins. In dehydrated rats the increase of neurohypophysial radioactivity during short time intervals after isotope injection exceeded that in controls, demonstrating an increased axonal transport due to osmotic stimuli. The turnover of rapidly as well as slowly transported neurohypophysial proteins was increased after dehydration but was decreased in water-loaded rats. After water deprivation or salt-loading with 2% NaCl solution for 7 days the neural lobe neurophysin was reduced in amount by 80–90%, whereas during salt-loading with 1% NaCl solution a 20% reduction was observed on the 14th as well as the 30th day. As judged from the amount of radioactivity in posterior pituitary neurophysin in dehydrated rats it is suggested that newly synthesized rapidly transported neurophysin is rapidly released after its arrival in the neural lobe.

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Angiotensin AT1A receptors expressed in vasopressin-producing cells of the supraoptic nucleus contribute to osmotic control of vasopressin

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00435.2017 ◽

2018 ◽

Vol 314 (6) ◽

pp. R770-R780 ◽

Cited By ~ 10

Author(s):

Jeremy A. Sandgren ◽

Danny W. Linggonegoro ◽

Shao Yang Zhang ◽

Sarah A. Sapouckey ◽

Kristin E. Claflin ◽

...

Keyword(s):

Supraoptic Nucleus ◽

Salt Intake ◽

Gene Encoding ◽

Conditional Allele ◽

Complex Stimuli ◽

Saline Loading ◽

Total Body ◽

The Brain ◽

Osmotic Stimuli

Angiotensin II (ANG) stimulates the release of arginine vasopressin (AVP) from the neurohypophysis through activation of the AT1 receptor within the brain, although it remains unclear whether AT1 receptors expressed on AVP-expressing neurons directly mediate this control. We explored the hypothesis that ANG acts through AT1A receptors expressed directly on AVP-producing cells to regulate AVP secretion. In situ hybridization and transgenic mice demonstrated localization of AVP and AT1A mRNA in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN), but coexpression of both AVP and AT1A mRNA was only observed in the SON. Mice harboring a conditional allele for the gene encoding the AT1A receptor (AT1Aflox) were then crossed with AVP-Cre mice to generate mice that lack AT1A in all cells that express the AVP gene (AT1AAVP-KO). AT1AAVP-KO mice exhibited spontaneously increased plasma and serum osmolality but no changes in fluid or salt-intake behaviors, hematocrit, or total body water. AT1AAVP-KO mice exhibited reduced AVP secretion (estimated by measurement of copeptin) in response to osmotic stimuli such as acute hypertonic saline loading and in response to chronic intracerebroventricular ANG infusion. However, the effects of these receptors on AVP release were masked by complex stimuli such as overnight dehydration and DOCA-salt treatment, which simultaneously induce osmotic, volemic, and pressor stresses. Collectively, these data support the expression of AT1A in AVP-producing cells of the SON but not the PVN, and a role for AT1A receptors in these cells in the osmotic regulation of AVP secretion.

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Disparate expression of the AVP gene in Sabra hypertension-prone and hypertension-resistant rats

AJP Renal Physiology ◽

10.1152/ajprenal.1996.271.4.f806 ◽

1996 ◽

Vol 271 (4) ◽

pp. F806-F813 ◽

Cited By ~ 5

Author(s):

C. Yagil ◽

D. Ben-Ishay ◽

Y. Yagil

Keyword(s):

Water Deprivation ◽

Selection Procedure ◽

Urine Osmolality ◽

Salt Sensitivity ◽

Salt Loading ◽

Water Handling ◽

Mrna Content ◽

Basal Plasma ◽

Rna Protection ◽

Avp Gene

We recently re-inbred the original colony of SBH-SBN rats, a model of salt-induced hypertension. In the course of phenotyping the new colony, SBH/y were found to excrete a lower urine flow with a higher urine osmolality than SBN/y. Thus disparate water handling between the substrains, a phenotype characteristic of the original colony, was retained throughout the selection procedure and transmitted down the generations to the new colony. As water handling is directly linked to arginine vasopressin (AVP) and in view of potential linkage of this phenotype to salt sensitivity or resistance in terms of the development of hypertension, the AVP axis was further investigated in the new substrains. Basal plasma AVP levels were higher in SBH/y (2.86 +/- 0.22 pg/ml; n = 10) than in SBN/y (1.98 +/- 0.11 pg/ml; n = 10, P < 0.05). Water deprivation for 48 h increased plasma AVP levels severalfold in both substrains to similar levels. Niravoline, a kappa receptor agonist that inhibits central release of AVP, produced at 0.6 and 0.9 mg/kg a more profound diuretic effect in SBN/y than in SBH/y, suggesting greater pituitary release of AVP into the circulation of SBH/y. AVP mRNA contents were compared in SBH/y and SBN/y rats in whole hypothalamic extracts and in the supraoptic (SON) and paraventricular (PVN) nuclei by RNA protection assay. Under basal conditions, AVP mRNA content (in ng) in the hypothalamus of SBH/y was 4.48 +/- 0.52 (n = 29) and of SBN/y was 3.13 +/- 0.35 (n = 30), P < 0.05; in the SON of SBH/y, AVP mRNA content was 3.62 +/- 0.44 (n = 11) and of SBN/y was 2.21 +/- 0.54 (n = 10), P < 0.05; in the PVN of SBH/y, AVP mRNA content was 0.78 +/- 0.16 (n = 9) and of SBN/y was 0.77 +/- 0.13 (n = 11, not significant). Thus the differences in hypothalamic AVP mRNA were primarily in the SON. Water deprivation as well as salt loading (8% NaCl) induced a significant elevation in AVP mRNA content in SBN/y but a blunted response in SBH/y. These data suggest that there is genetically transmitted enhanced hypothalamic expression of the AVP gene in SBH/y compared with SBN/y which results, under basal conditions, in greater pituitary release of AVP, in higher plasma AVP levels, and in increased renal concentrating activity. As AVP has been implicated in various forms of hypertension, these findings render AVP a candidate gene for salt sensitivity or resistance in the Sabra rat model of hypertension.

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Brain Evidence in Nursing Research: EEG Methodology

International Annals of Science ◽

10.21467/ias.10.1.98-101 ◽

2020 ◽

Vol 10 (1) ◽

pp. 98-101

Author(s):

Yueh-O Chuang ◽

Ren-Jen Hwang

Keyword(s):

Emotional Health ◽

Physiological Data ◽

Evidence Based ◽

Nursing Research ◽

Healthy Behaviors ◽

Alpha Asymmetry ◽

Role Of Nursing ◽

Brain Behavior ◽

Evidence Based Nursing ◽

The Brain

This aim of the mini-review paper is to introduction the bio-physiologic measures of resting state EEG for nursing scientist. Article specifically addresses the emotional domain as clarified by concepts of brain evidence-based nursing research reviewed that the emotion aspect documented a strong link to frontal brain alpha activities asymmetry. Extensive nursing research has been performed in emotional, behavioral, and/or psychological matters for healthy and unhealthy populations. Evidence-based nursing can transform the way that data is used to improve health and healthcare. One core role of nursing practice is to promote healthy behaviors. Previous researches have shown out that the brain is the main ambassador of behavioral change. The electroencephalogram (EEG) is an efficient tool to study brain-behavior relations. Evidences show that frontal alpha asymmetry is an important marker suggests that EEG is beneficial for assessment emotional capacities and appraises nursing efficiency. The basic resting alpha frontal asymmetry provides a reliable instrument in conducting nursing researches in order to strengthen the quality of nursing. Furthermore, we provide a viewpoint to show progress in the novel research issue probably for clinical applications. To integrate biological measures in order to gain highly accurate and precise advantages of EEG and beneficial assessment of the emotional capacities are suggested. Nursing promotes healthy behaviors including emotional health. Human behavior changes originate in the brain. EEG enables objective and biological insights into the cognitive process. As a foundation, the neuroscience research requires profound knowledge and tools to analyze bio-physiological data. Creating Cross-disciplinary cooperation must be inevitable alliances to advance nursing research.

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Miniaturization and Automation of a Human In Vitro Blood–Brain Barrier Model for the High-Throughput Screening of Compounds in the Early Stage of Drug Discovery

Pharmaceutics ◽

10.3390/pharmaceutics13060892 ◽

2021 ◽

Vol 13 (6) ◽

pp. 892

Author(s):

Elisa L. J. Moya ◽

Elodie Vandenhaute ◽

Eleonora Rizzi ◽

Marie-Christine Boucau ◽

Johan Hachani ◽

...

Keyword(s):

Drug Discovery ◽

Blood Brain Barrier ◽

Early Stage ◽

Molecular Transport ◽

Brain Barrier ◽

Blood Brain ◽

Cns Drugs ◽

The Impact ◽

The Brain

Central nervous system (CNS) diseases are one of the top causes of death worldwide. As there is a difficulty of drug penetration into the brain due to the blood–brain barrier (BBB), many CNS drugs treatments fail in clinical trials. Hence, there is a need to develop effective CNS drugs following strategies for delivery to the brain by better selecting them as early as possible during the drug discovery process. The use of in vitro BBB models has proved useful to evaluate the impact of drugs/compounds toxicity, BBB permeation rates and molecular transport mechanisms within the brain cells in academic research and early-stage drug discovery. However, these studies that require biological material (animal brain or human cells) are time-consuming and involve costly amounts of materials and plastic wastes due to the format of the models. Hence, to adapt to the high yields needed in early-stage drug discoveries for compound screenings, a patented well-established human in vitro BBB model was miniaturized and automated into a 96-well format. This replicate met all the BBB model reliability criteria to get predictive results, allowing a significant reduction in biological materials, waste and a higher screening capacity for being extensively used during early-stage drug discovery studies.

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The Impact of Bone on the Biology of Aging

Innovation in Aging ◽

10.1093/geroni/igaa057.2643 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 740-740

Author(s):

Gerard Karsenty

Keyword(s):

Muscle Function ◽

Male Fertility ◽

Leydig Cells ◽

Memory Loss ◽

Age Related ◽

Systematic Exploration ◽

Biology Of Aging ◽

The Impact ◽

The Brain ◽

Regulate Energy Metabolism

Abstract We hypothesized that bone may secrete hormones that regulate energy metabolism and reproduction. Testing this hypothesis revealed that the osteoblast-specific secreted protein osteocalcin is a hormone regulating glucose homeostasis and male fertility by signaling through a GPCR, Gprc6a, expressed in pancreatic β bells and Leydig cells of the testes. The systematic exploration of osteocalcin biology, revealed that it regulates an unexpectedly large spectrum of physiological functions in the brain and peripheral organs and that it has most features of an antigeromic molecule. As will be presented at the meeting, this body of work suggests that harnessing osteocalcin for therapeutic purposes may be beneficial in the treatment of age-related diseases such as depression, age-related memory loss and the decline in muscle function seen in sarcopenia.

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Crosstalk between Existential Phenomenological Psychotherapy and Neurological Sciences in Mood and Anxiety Disorders

Biomedicines ◽

10.3390/biomedicines9040340 ◽

2021 ◽

Vol 9 (4) ◽

pp. 340

Author(s):

Lehel Balogh ◽

Masaru Tanaka ◽

Nóra Török ◽

László Vécsei ◽

Shigeru Taguchi

Keyword(s):

Anxiety Disorders ◽

Biological Treatment ◽

Sense Of Self ◽

Phenomenological Approach ◽

Neurological Damage ◽

Mood And Anxiety Disorders ◽

New Interpretation ◽

And Behavior ◽

The Impact ◽

The Brain

Psychotherapy is a comprehensive biological treatment modifying complex underlying cognitive, emotional, behavioral, and regulatory responses in the brain, leading patients with mental illness to a new interpretation of the sense of self and others. Psychotherapy is an art of science integrated with psychology and/or philosophy. Neurological sciences study the neurological basis of cognition, memory, and behavior as well as the impact of neurological damage and disease on these functions, and their treatment. Both psychotherapy and neurological sciences deal with the brain; nevertheless, they continue to stay polarized. Existential phenomenological psychotherapy (EPP) has been in the forefront of meaning-centered counseling for almost a century. The phenomenological approach in psychotherapy originated in the works of Martin Heidegger, Ludwig Binswanger, Medard Boss, and Viktor Frankl, and it has been committed to accounting for the existential possibilities and limitations of one’s life. EPP provides philosophically rich interpretations and empowers counseling techniques to assist mentally suffering individuals by finding meaning and purpose to life. The approach has proven to be effective in treating mood and anxiety disorders. This narrative review article demonstrates the development of EPP, the therapeutic methodology, evidence-based accounts of its curative techniques, current understanding of mood and anxiety disorders in neurological sciences, and a possible converging path to translate and integrate meaning-centered psychotherapy and neuroscience, concluding that the EPP may potentially play a synergistic role with the currently prevailing medication-based approaches for the treatment of mood and anxiety disorders.

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