Comparison of dipsogenic responses of adult offspring as a function of different perinatal programming models

The perinatal environment interacts with the genotype of the developing organism resulting in a unique phenotype through a developmental or perinatal programming phenomenon. However, it remains unclear how this phenomenon differentially affects particular targets expressing specific drinking responses depending on the perinatal conditions. The main goal of the present study was to compare the dipsogenic responses induced by different thirst models as a function of two perinatal manipulation models, defined by the maternal free access to hypertonic sodium solution and a partial aortic ligation (PAL-W/Na) or a sham-ligation (Sham-W/Na). The programmed adult offspring of both perinatal manipulated models responded similarly when was challenged by overnight water dehydration or after a sodium depletion showing a reduced water intake in comparison to the non-programmed animals. However, when animals were evaluated after a body sodium overload, only adult Sham-W/Na offspring showed drinking differences compared to PAL and control offspring. By analyzing the central neurobiological substrates involved, a significant increase in the number of Fos + cells was found after sodium depletion in the subfornical organ of both programmed groups and an increase in the number of Fos + cells in the dorsal raphe nucleus was only observed in adult depleted PAL-W/Na. Our results suggest that perinatal programming is a phenomenon that differentially affects particular targets which induce specific dipsogenic responses depending on matching between perinatal programming conditions and the osmotic challenge in the latter environment. Probably, each programmed-drinking phenotype has a particular set point to elicit specific repertoires of mechanisms to reestablish fluid balance.

Growth failure and metabolic acidosis due to total body sodium depletion in an infant with an ileostomy

Sodium is an essential nutrient and inadequate sodium intake and/or excessive sodium losses can result in suboptimal growth. Infants with ileostomies are at significant risk of developing growth failure as a result of excessive sodium loss in their ileostomy effluent. Chronic sodium depletion can also limit the kidney’s ability to excrete hydrogen and potassium ions, mimicking electrolyte abnormalities found in type 4 renal tubular acidosis. This report describes an infant with an ileostomy with severe growth failure, hyperkalaemia and metabolic acidosis—all of which promptly resolved with sodium supplementation.

Pre-locus coeruleus neurons in rat and mouse

Previously, we identified a population of neurons in the hindbrain tegmentum, bordering the locus coeruleus (LC). We named this population the pre-locus coeruleus (pre-LC) because in rats its neurons lie immediately rostral to the LC. In mice, however, pre-LC and LC neurons intermingle, making them difficult to distinguish. Here we use molecular markers and anterograde tracing to clarify the location and distribution of pre-LC neurons in mice, relative to rats. First, we co-localized the transcription factor FoxP2 with the activity marker Fos to identify pre-LC neurons in sodium-deprived rats and show their distribution relative to surrounding catecholaminergic and cholinergic neurons. Next, we used sodium depletion and chemogenetic activation of the aldosterone-sensitive HSD2 neurons in the nucleus of the solitary tract (NTS) to identify the homologous population of pre-LC neurons in mice, along with a related population in the central lateral parabrachial nucleus. Using Cre-reporter mice for Pdyn, we confirmed that most of these sodium-depletion-activated neurons are dynorphinergic. Finally, after confirming that these neurons receive excitatory input from the NTS and paraventricular hypothalamic nucleus, plus convergent input from the inhibitory AgRP neurons in the arcuate hypothalamic nucleus, we identify a major, direct input projection from the medial prefrontal cortex. This new information on the location, distribution, and input to pre-LC neurons provides a neuroanatomical foundation for cell-type-specific investigation of their properties and functions in mice. Pre-LC neurons likely integrate homeostatic information from the brainstem and hypothalamus with limbic, contextual information from the cerebral cortex to influence ingestive behavior.

Physiological and Transcriptomic Changes in the Hypothalamic-Neurohypophysial System after 24 h of Furosemide-Induced Sodium Depletion

<b><i>Background/Aims:</i></b> Furosemide is a loop diuretic widely used in clinical practice for the treatment of oedema and hypertension. The aim of this study was to determine physiological and molecular changes in the hypothalamic-neurohypophysial system as a consequence of furosemide-induced sodium depletion. <b><i>Methods:</i></b> Male rats were sodium depleted by acute furosemide injection (10 and 30 mg/kg) followed by access to low sodium diet and distilled water for 24 h. The renal and behavioural consequences were evaluated, while blood and brains were collected to evaluate the neuroendocrine and gene expression responses. <b><i>Results:</i></b> Furosemide treatment acutely increases urinary sodium and water excretion. After 24 h, water and food intake were reduced, while plasma angiotensin II and corticosterone were increased. After hypertonic saline presentation, sodium-depleted rats showed higher preference for salt. Interrogation using RNA sequencing revealed the expression of 94 genes significantly altered in the hypothalamic paraventricular nucleus (PVN) of sodium-depleted rats (31 upregulated and 63 downregulated). Out of 9 genes chosen, 5 were validated by quantitative PCR in the PVN (upregulated: Ephx2, Ndnf and Vwf; downregulated: Caprin2 and Opn3). The same genes were also assessed in the supraoptic nucleus (SON, upregulated: Tnnt1, Mis18a, Nr1d1 and Dbp; downregulated: Caprin2 and Opn3). As a result of these plastic transcriptome changes, vasopressin expression was decreased in PVN and SON, whilst vasopressin and oxytocin levels were reduced in plasma. <b><i>Conclusions:</i></b> We thus have identified novel genes that might regulate vasopressin gene expression in the hypothalamus controlling the magnocellular neurons secretory response to body sodium depletion and consequently hypotonic stress.

Static Leaching and Alteration Mechanisms of Zirconium Alkali Resistant Glasses Containing Heavy Metals

The aim of this study is to understand mechanisms that occur during leaching of alkali-resistant zirconium-containing glasses in acid and alkaline solutions. For this, we have developed 5 glass compositions: two alkali-resistant model glasses type CEMFIL, V1 (with zirconium and without heavy metals) and V2 (with zirconium and heavy metals), then three glasses of fly ashes V3 (without zirconium and with heavy metals), V4 (with 30 % of V3, zirconium and heavy metals) and V5 (with 60% of V3, zirconium and heavy metals). V4 and V5 are obtained using V3 as raw material and supplementing with SiO2, ZrO2 and Na2O to give them alkali-resistant properties. Glasses leaching in acidic and basic medium led to an important basification from the first times of alteration at pH = 4 when a basification decrease is observed for solutions initially at pH = 13. Normalized elementary mass losses results showed that, glass alteration is higher for low-calcium glasses (V1 and V2) and V4 and V5 glasses have the lowest elemental mass losses at pH = 4 and 13. SIMS profiles made on glass alteration films permitted to observe behaviour of H, Na, Ca, Si and Zr elements after 28 days at pH = 4 and 13 and understand the different dissolution mechanisms involved. SIMS profiles showed that a hydrated film develops on glass surface characterized by hydrogen enrichment and sodium depletion irrespective of the glass. These glasses are also characterized by a surface enrichment of zirconium (except V3 which does not contain zirconium) whatever the pH. Hydrated film thickness confirm that V1, V2 and V3 glasses are more altered than V4 and V5 glasses. These results are confirmed by ICP-AES leachate analysis.

Cortisol and Aldosterone Responses to Hypoglycemia and Na Depletion in Women With Non-Classic 21-Hydroxylase Deficiency

Background Non-classic 21-hydroxylase deficiency is usually diagnosed in post-pubertal women because of androgen excess. Indication of systematic steroid replacement therapy is controversial because the risk of acute adrenal insufficiency is unknown. In order to specify this risk we evaluated the cortisol and aldosterone secretions in response to appropriate pharmacologic challenges. Methods In this prospective case–control non-inferiority study we investigated 20 women with non-classic 21-hydroxylase deficiency carrying biallelic CYP21A2 mutations and with serum 17-hydroxyprogesterone (17OHP) &gt;10 ng/mL after stimulation with Synacthen® (tetracosactrin) and 20 age- and body mass index-matched healthy women with 17OHP after Synacthen® &lt;2 ng/mL. Each participant underwent sequentially an insulin tolerance test to evaluate cortisol secretion and a sodium depletion test, obtained by oral administration of 40 mg of furosemide under low sodium diet (&lt;20 mmol during 24 hours), to evaluate renin and aldosterone secretion. Findings The peak serum cortisol concentration after insulin hypoglycemia was lower in patients than in controls (mean difference –47 ng/mL, 90% CI, –66, P = 0.0026). A peak serum cortisol above a cutoff value of 170 ng/mL was obtained in all controls but only in 55% of patients (P = 0.0039). Twenty-four hours after sodium depletion, blood pressure, plasma sodium, potassium, and serum aldosterone concentrations were comparable between the two groups, but patients had higher stimulated renin concentrations than controls (P = 0.0044). Interpretation Patients with non-classic 21-hydroxylase deficiency frequently display partial cortisol insufficiency and compensated defect in aldosterone secretion. Their clinical management should systematically include assessment of adrenal functions.