scholarly journals DREADD-induced activation of subfornical organ neurons stimulates thirst and salt appetite

2016 ◽  
Vol 115 (6) ◽  
pp. 3123-3129 ◽  
Author(s):  
Haley L. Nation ◽  
Marvin Nicoleau ◽  
Brian J. Kinsman ◽  
Kirsteen N. Browning ◽  
Sean D. Stocker
Keyword(s):  
Water Intake ◽  
Body Fluid ◽  
Subfornical Organ ◽  
Designer Drugs ◽  
Salt Appetite ◽  
Fluid Homeostasis ◽  
Body Fluid Homeostasis ◽  
Acute Injection

The subfornical organ (SFO) plays a pivotal role in body fluid homeostasis through its ability to integrate neurohumoral signals and subsequently alter behavior, neuroendocrine function, and autonomic outflow. The purpose of the present study was to evaluate whether selective activation of SFO neurons using virally mediated expression of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) stimulated thirst and salt appetite. Male C57BL/6 mice (12–15 wk) received an injection of rAAV2-CaMKII-HA-hM3D(Gq)-IRES-mCitrine targeted at the SFO. Two weeks later, acute injection of clozapine N-oxide (CNO) produced dose-dependent increases in water intake of mice with DREADD expression in the SFO. CNO also stimulated the ingestion of 0.3 M NaCl. Acute injection of CNO significantly increased the number of Fos-positive nuclei in the SFO of mice with robust DREADD expression. Furthermore, in vivo single-unit recordings demonstrate that CNO significantly increases the discharge frequency of both ANG II- and NaCl-responsive neurons. In vitro current-clamp recordings confirm that bath application of CNO produces a significant membrane depolarization and increase in action potential frequency. In a final set of experiments, chronic administration of CNO approximately doubled 24-h water intake without an effect on salt appetite. These findings demonstrate that DREADD-induced activation of SFO neurons stimulates thirst and that DREADDs are a useful tool to acutely or chronically manipulate neuronal circuits influencing body fluid homeostasis.

Stanniocalcin-1 in the subfornical organ inhibits the dipsogenic response to angiotensin II

2012 ◽  
Vol 303 (9) ◽  
pp. R921-R928 ◽  
Author(s):  
Jason M. Moreau ◽  
Waseem Iqbal ◽  
Jeffrey K. Turner ◽  
Graham F. Wagner ◽  
John Ciriello
Keyword(s):  
Western Blot ◽  
Water Intake ◽  
Body Fluid ◽  
Physiological Role ◽  
Subfornical Organ ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Glycoprotein Hormone ◽  
Fluid Homeostasis ◽  
Body Fluid Homeostasis

Recently, receptors for the calcium-regulating glycoprotein hormone stanniocalcin-1 (STC-1) have been found within subfornical organ (SFO), a central structure involved in the regulation of electrolyte and body fluid homeostasis. However, whether SFO neurons produce STC-1 and how STC-1 may function in fluid homeostasis are not known. Two series of experiments were done in Sprague-Dawley rats to investigate whether STC-1 is expressed within SFO and whether it exerts an effect on water intake. In the first series, experiments were done to determine whether STC-1 was expressed within cells in SFO using immunohistochemistry, and whether protein and gene expression for STC-1 existed in SFO using Western blot and quantitative RT-PCR, respectively. Cells containing STC-1 immunoreactivity were found throughout the rostrocaudal extent of SFO. STC-1 protein expression within SFO was confirmed with Western blot, and SFO was also found to express STC-1 mRNA. In the second series, microinjections (200 nl) of STC-1, ANG II, a combination of the two or the vehicle were made into SFO in conscious, unrestrained rats. Water intake was measured at 0700 for a 1-h period after each injection in animals. Microinjections of STC-1 (17.6 or 176 nM) alone had no effect on water intake compared with controls. However, STC-1 not only attenuated the drinking responses to ANG II for about 30 min, but also decreased the total water intake over the 1-h period. These data suggest that STC-1 within the SFO may act in a paracrine/autocrine manner to modulate the neuronal responses to blood-borne ANG II. These findings also provide the first direct evidence of a physiological role for STC-1 in central regulation of body fluid homeostasis.

scholarly journals AT1a influences GABAA-mediated inhibition through regulation of KCC2 expression

2018 ◽  
Vol 315 (5) ◽  
pp. R972-R982 ◽  
Author(s):  
George E. Farmer ◽  
Kirthikaa Balapattabi ◽  
Martha E. Bachelor ◽  
Joel T. Little ◽  
J. Thomas Cunningham
Keyword(s):  
Protein Expression ◽  
Body Fluid ◽  
Neuronal Excitability ◽  
Receptor Activation ◽  
Cardiovascular Control ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Fluid Homeostasis ◽  
Body Fluid Homeostasis

The median preoptic nucleus (MnPO) is an integrative site involved in body fluid homeostasis, cardiovascular control, thermoregulation, and sleep homeostasis. Angiotensin II (ANG II), a neuropeptide shown to have excitatory effects on MnPO neurons, is of particular interest with regard to its role in body fluid homeostasis and cardiovascular control. The present study investigated the role of angiotensin type 1a (AT1a) receptor activation on neuronal excitability in the MnPO. Male Sprague-Dawley rats were infused with an adeno-associated virus with an shRNA against the AT1a receptor or a scrambled control. In vitro loose-patch voltage-clamp recordings of spontaneous action potential activity were made from labeled MnPO neurons in response to brief focal application of ANG II or the GABAA receptor agonist muscimol. Additionally, tissue punches from MnPO were taken to asses mRNA and protein expression. AT1a receptor knockdown neurons were insensitive to ANG II and showed a marked reduction in GABAA-mediated inhibition. The reduction in GABAA-mediated inhibition was not associated with reductions in mRNA or protein expression of GABAA β-subunits. Knockdown of the AT1a receptor was associated with a reduction in the potassium-chloride cotransporter KCC2 mRNA as well as a reduction in pS940 KCC2 protein. The impaired GABAA-mediated inhibition in AT1a knockdown neurons was recovered by bath application of phospholipase C and protein kinase C activators. The following study indicates that AT1a receptor activation mediates the excitability of MnPO neurons, in part, through the regulation of KCC2. The regulation of KCC2 influences the intracellular [Cl−] and the subsequent efficacy of GABAA-mediated currents.

Functional relationship between subfornical organ cholinergic stimulation and nitrergic activation influencing cardiovascular and body fluid homeostasis

2007 ◽  
Vol 143 (1-3) ◽  
pp. 28-33 ◽  
Author(s):  
Wilson Abrão Saad ◽  
Ismael Francisco Motta Siqueira Guarda ◽  
Luis Antonio de Arruda Camargo ◽  
Talmir Augusto Faria Brisola dos Santos ◽  
William Abrão Saad
Keyword(s):  
Body Fluid ◽  
Functional Relationship ◽  
Subfornical Organ ◽  
Cholinergic Stimulation ◽  
Fluid Homeostasis ◽  
Body Fluid Homeostasis

Abstract 017: Optogenetic Activation of OVLT Neurons Stimulates Water Intake and Produces a Sympathetically-Mediated Increase in Arterial Blood Pressure

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Sean D Stocker ◽  
Sarah S Simmonds
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Arterial Blood Pressure ◽  
Water Intake ◽  
Body Fluid ◽  
Frequency Dependent ◽  
Fluid Homeostasis ◽  
Direct Activation ◽  
Arterial Blood ◽  
Body Fluid Homeostasis

The organum vasculosum of the lamina terminalis (OVLT) plays a pivotal role in body fluid homeostasis and arterial blood pressure (ABP) regulation. The OVLT lacks a complete blood-brain-barrier and responds to an array of circulating factors such as NaCl and angiotensin II. Lesion of the anteroventral third ventricular region which includes the OVLT attenuates or reverses several forms of salt-sensitive hypertension. However, there is limited evidence to demonstrate that direct activation of OVLT neurons alters body fluid homeostasis or elevates ABP. To address this question, Male-Sprague-Dawley rats (300-350 g) received an injection of rAAV9-CamKII-hChR2(H134R)-EYFP (10 12 particles/mL, 200nL) into the OVLT. A fiber optic cannula (200μm) was implanted 300μm dorsal to OVLT. Approximately 2-3 week later, optogenetic activation of OVLT neurons (10ms pulse, 50% duty cycle, 30 min) produced frequency-dependent increases in water intake (1Hz: 1.0±0.5mL; 5Hz: 4.2±0.6mL; 10Hz: 8.0±1.8; 20Hz: 10.2±2.1mL, n=4, P<0.05). In separate experiments, optogenetic activation of OVLT neurons produced a frequency-dependent increase in mean ABP (1Hz: 1±1 mmHg; 5Hz: 3±1mmHg; 10Hz: 7±1mmHg; 20Hz: 13±1mmHg, n=4, P<0.05) and heart rate (1Hz: 3±6 bpm; 5Hz: 15±5bpm; 10Hz: 40±12 bpm; 20Hz: 62±14bpm, n=4, P<0.05). Pretreatment with the vasopressin antagonist Manning Compound (10ug/kg, IV) did not affect these responses. However, pretreatment with the ganglionic blocker chlorisondamine (5mg/kg, IV) abolished the pressor (20Hz: 1±1 mmHg, P<0.01) and tachycardic (20Hz: 4±7 bpm, P<0.05) responses to activation of OVLT neurons. Finally, in vivo single-unit recordings demonstrate that optogenetic activation produced frequency-dependent increases in cell discharge of OVLT neurons responsive to either intracarotid injection of hypertonic NaCl (0.3M NaCl, 50μL over 10 s, n=6) or angiotensin II (100ng over 10s, n=3). Collectively, these data provide evidence that direct activation of OVLT neurons stimulates thirst and produces a sympathetically-mediated increase in ABP.

scholarly journals Apelin and Vasopressin: The Yin and Yang of Water Balance

2021 ◽  
Vol 12 ◽  
Author(s):  
Pierre-Emmanuel Girault-Sotias ◽  
Romain Gerbier ◽  
Adrien Flahault ◽  
Nadia de Mota ◽  
Catherine Llorens-Cortes
Keyword(s):  
Body Fluid ◽  
Collecting Duct ◽  
Plasma Osmolality ◽  
Receptor Activation ◽  
Fluid Homeostasis ◽  
Antidiuretic Effect ◽  
Body Fluid Homeostasis ◽  
Yin And Yang ◽  
Apelin Receptor

Apelin, a (neuro)vasoactive peptide, plays a prominent role in controlling body fluid homeostasis and cardiovascular functions. Experimental data performed in rodents have shown that apelin has an aquaretic effect via its central and renal actions. In the brain, apelin inhibits the phasic electrical activity of vasopressinergic neurons and the release of vasopressin from the posterior pituitary into the bloodstream and in the kidney, apelin regulates renal microcirculation and counteracts in the collecting duct, the antidiuretic effect of vasopressin occurring via the vasopressin receptor type 2. In humans and rodents, if plasma osmolality is increased by hypertonic saline infusion/water deprivation or decreased by water loading, plasma vasopressin and apelin are conversely regulated to maintain body fluid homeostasis. In patients with the syndrome of inappropriate antidiuresis, in which vasopressin hypersecretion leads to hyponatremia, the balance between apelin and vasopressin is significantly altered. In order to re-establish the correct balance, a metabolically stable apelin-17 analog, LIT01-196, was developed, to overcome the problem of the very short half-life (in the minute range) of apelin in vivo. In a rat experimental model of vasopressin-induced hyponatremia, subcutaneously (s.c.) administered LIT01-196 blocks the antidiuretic effect of vasopressin and the vasopressin-induced increase in urinary osmolality, and induces a progressive improvement in hyponatremia, suggesting that apelin receptor activation constitutes an original approach for hyponatremia treatment.

In Vitro and In Vivo Degradation, Mechanical Properties, and Histocompatibility of Weft-Knitted Silk Mesh-Like Grafts

2022 ◽  
Vol 12 (2) ◽  
pp. 411-416
Author(s):  
Liang Tang ◽  
Si-Yu Zhao ◽  
Ya-Dong Yang ◽  
Geng Yang ◽  
Wen-Yuan Zhang ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Simulated Body Fluid ◽  
Body Fluid ◽  
Degradation Rate ◽  
Maximum Load ◽  
Artificial Ligament ◽  
In Vivo Degradation

To investigate the degradation, mechanical properties, and histocompatibility of weft-knitted silk mesh-like grafts, we carried out the In Vitro and In Vivo silk grafts degradation assay. The In Vitro degradation experiment was performed by immersing the silk grafts in simulated body fluid for 1 year, and the results showed that the degradation rate of the silk mesh-like grafts was very slow, and there were few changes in the mechanical properties and quality of the silk mesh-like graft. In Vivo degradation assay was taken by implantation of the silk mesh-like grafts into the subcutaneous muscles of rabbits. At 3, 6, and 12 months postoperation, the rate of mass loss was 19.36%, 31.84%, and 58.77%, respectively, and the maximum load was 63.85%, 34.63%, and 10.76%, respectively of that prior to degradation. The results showed that the degradation rate of the silk graft and the loss of mechanical properties In Vivo were faster than the results obtained in the In Vitro experiments. In addition, there were no significant differences in secretion of serum IL-6 and TNF-α between the experimental and normal rabbits (P >0.05), suggesting no obvious inflammatory reaction. The findings suggest that the weft-knitted silk mesh-like grafts have good mechanical properties, histocompatibility, and In Vivo degradation rate, and therefore represent a candidate material for artificial ligament

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