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

Dutra, Sabrina Graziani Veloso; Paterson, Alex; Monteiro, Livia R.N.; Greenwood, Michael; Greenwood, Mingkwan; Amaral, Ludimila Santos; Melo, Mariana; Colombari, Débora S. A.; Colombari, Eduardo; Reis, L. C.; Hindmarch, Charles C.T.; Elias, Lucila Leico Kagohara; Antunes‐Rodrigues, José; Murphy, David; Mecawi, André Souza

doi:10.1159/000505997

Cited by 19 publications

(19 citation statements)

References 56 publications

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“…9B). RNA-seq has suggested that OPN3 is present in the supraoptic nucleus (Dutra et al, 2020), a region where we also found high OPN3-mCh expression. Additionally, Figure 10.…”

Section: Thalamus and Hypothalamussupporting

confidence: 71%

“…In the hypothalamus, OPN3 mRNA was initially identified in the PVH and medial preoptic area (MPA) by RNA-seq (Dutra et al, 2020), Western blotting, and immunostaining (Nissilä et al, 2012). We confirmed that OPN3-mCh was expressed in the MPA and highly expressed in the PVH (Fig.…”

Section: Thalamus and Hypothalamussupporting

confidence: 67%

“…While the distribution of encephalic OPN3 mRNA has previously been examined (Blackshaw and Snyder, 1999;Halford et al, 2001;Dutra et al, 2020) and OPN3 expression for some brain regions has been studied using promoter-driven GFP reporter mice (GENSAT; Gong et al, 2003) and immunostaining (Nissilä et al, 2012;El Massri et al, 2018), our analysis of OPN3-mCh expression from coronal, sagittal, and horizontal planes across the adult OPN3-mCh brain has uncovered novel findings. We have first identified new regions in the brain in which OPN3 expression was previously unknown including: mitral cell layer, piriform area and nucleus of the lateral olfactory tract of the olfactory areas; CA regions and presubiculum of the HCF; posterior hypothalamic nucleus; inferior colliculus, and nucleus sagulum of the midbrain; and pontine gray and superior olivary complex in the pons (Extended Data Fig.…”

Section: Discussionmentioning

confidence: 97%

See 2 more Smart Citations

Endogenous Opsin 3 (OPN3) Protein Expression in the Adult Brain Using a Novel OPN3-mCherry Knock-In Mouse Model

Olinski

Tsuda

Kauer

et al. 2020

eNeuro

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The opsins have been studied extensively for their functions in visual phototransduction; however, the mechanisms underlying extraocular opsin signaling remain poorly understood. The first mammalian extraocular opsin to be discovered, opsin 3 (OPN3), was found in the brain more than two decades ago, yet its function remains unknown. A significant hindrance to studying OPN3 has been a lack of specific antibodies against mammalian OPN3, resulting in an incomplete understanding of its expression in the brain. Although Opn3 promoter-driven reporter mice have been generated to examine general OPN3 localization, they lack the regulated expression of the endogenous protein and the ability to study its subcellular localization. To circumvent these issues, we have created a knock-in OPN3-mCherry mouse model in which the fusion protein OPN3-mCherry is expressed Significance Statement Before the current report, there had been a significant lack of encephalic opsin 3 (OPN3) protein characterization, likely driven by the absence of murine OPN3 antibodies. This study describes a novel OPN3-mCherry knock-in mouse that we used to analyze endogenous OPN3 protein expression across the brain. We have uncovered new aspects of OPN3: localization to previously undocumented brain subregions, expression in GABAergic neurons and non-neuronal cells, and punctate subcellular localization in the soma. Our OPN3 expression map is an invaluable step toward discovering its elusive encephalic functions. The OPN3-mCherry mouse will facilitate investigation of OPN3 not only in the brain, but also across the entire organism, a useful feature as OPN3 is emerging as a possible mediator of phototransduction outside the brain.

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“…9B). RNA-seq has suggested that OPN3 is present in the supraoptic nucleus (Dutra et al, 2020), a region where we also found high OPN3-mCh expression. Additionally, Figure 10.…”

Section: Thalamus and Hypothalamussupporting

confidence: 71%

Section: Thalamus and Hypothalamussupporting

confidence: 67%

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Endogenous Opsin 3 (OPN3) Protein Expression in the Adult Brain Using a Novel OPN3-mCherry Knock-In Mouse Model

Olinski

Tsuda

Kauer

et al. 2020

eNeuro

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“…Conversely, the use of loop diuretics as a cause for sodium depletion is highly likely, as the prescribed furosemide dosage was higher among hyponatremic CRS patients in comparison to non-hyponatremic ones. In addition to sodium depletion, loop diuretics induce a hypovolemia-triggered, appropriate AVP activation [30].…”

Section: Hypovolemia As a Main Cause Of Hyponatremia In Hospitalized mentioning

confidence: 99%

Diabetes prevalence and outcomes in hospitalized cardiorenal-syndrome patients with and without hyponatremia

et al. 2020

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Background Hyponatremia is known to be associated with a worse patient outcome in heart failure. In cardiorenal syndrome (CRS), the prognostic role of concomitant hyponatremia is unclear. We sought to evaluate potential risk factors for hyponatremia in patients with CRS presenting with or without hyponatremia on hospital admission. Methods In a retrospective study, we investigated 262 CRS patients without sepsis admitted to the University Hospital Halle over a course of 4 years. CRS diagnosis was derived from an electronic search of concomitant diagnoses of acute or chronic (NYHA 3–4) heart failure and acute kidney injury (AKIN 1–3) or chronic kidney disease (KDIGO G3-G5nonD). A verification of CRS diagnosis was done based on patient records. Depending on the presence (Na < 135 mmol/L) or absence (Na ≥ 135 mmol/L) of hyponatremia on admission, the CRS patients were analyzed for comorbidities such as diabetes, presence of hypovolemia on admission, need for renal replacement therapy and prognostic factors such as in-hospital and one-year mortality. Results Two hundred sixty-two CRS patients were included in this study, thereof, 90 CRS patients (34.4%) with hyponatremia (Na < 135 mmol/L). The diabetes prevalence among CRS patients was high (> 65%) and not related to the serum sodium concentration on admission. In comparison to non-hyponatremic CRS patients, the hyponatremic patients had a lower serum osmolality, hypovolemia was more prevalent (41.1% versus 16.3%, p < 0.001). As possible causes of hypovolemia, diarrhea, a higher number of diuretic drug classes and higher diuretic dosages were found. Hyponatremic and non-hyponatremic CRS patients had a comparable need for renal-replacement therapy (36.7% versus 31.4%) during the hospital stay. However, after discharge, relatively more hyponatremic CRS patients on renal replacement therapy switched to a non-dialysis therapy regimen (50.0% versus 22.2%). Hyponatremic CRS patients showed a trend for a higher in-hospital mortality (15.6% versus 7.6%, p = 0.054), but no difference in the one-year mortality (43.3% versus 40.1%, p = 0.692). Conclusions All CRS patients showed a high prevalence of diabetes mellitus and a high one-year mortality. In comparison to non-hyponatremic CRS patients, hyponatremic ones were more likely to have hypovolemia, and had a higher likelihood for temporary renal replacement therapy.

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“…The latter was excluded for the patients of the current study. Conversely, the use of loop diuretics as a cause for sodium depletion is highly likely 28 , as the prescribed furosemide dosage was higher among hyponatremic CRS patients in comparison to non-hyponatremic ones. In addition to sodium depletion, loop diuretics induce a hypovolemiatriggered, appropriate AVP activitation 28 .…”

Section: Hypovolemia As a Main Cause Of Hyponatremia In Hospitalized mentioning

confidence: 99%

High prevalence of diabetes mellitus in hospitalized cardiorenal-syndrome patients with and without hyponatremia.

Pliquett¹,

Schlump²,

Wienke³

et al. 2020

Preprint

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Background Cardiorenal syndrome (CRS) defined as concurrent acute or chronic heart failure and acute or chronic kidney injury or disease frequently coincides with hyponatremia. We sought to identify potential risk factors for and outcome of hyponatremia in CRS. Methods In this retrospective study, CRS patients being consecutively hospitalized over 4 years (Department of Internal Medicine II, Martin-Luther University Halle-Wittenberg, Germany) were included. Depending on the presence or absence of hyponatremia on admission, they were analyzed for diabetes comorbidity, signs of hypovolemia on admission, need for renal replacement therapy during and after the hospital stay, in-hospital and one-year mortality. Results 262 CRS patients were included in this study, thereof, 90 CRS patients (34.4%) with hyponatremia (Na <135 mmol/L). The diabetes prevalence among CRS patients was high (>65%) and not related to the serum sodium concentration on admission. In comparison to non-hyponatremic CRS patients, the hyponatremic ones had a lower serum osmolality (293 versus 303 mosm/kg, p<0.001), and hypovolemia was more prevalent (41.1% versus 16.3%, p<0.001). As possible causes of hypovolemia, diarrhea, a higher number of diuretic drug classes and higher diuretic dosages were found. Hyponatremic and non-hyponatremic CRS patients had a comparable need for renal-replacement therapy (36.7% versus 31.4%) during the hospital stay. However, after discharge, relatively more hyponatremic CRS patients on renal replacement therapy switched to a non-dialysis, medical therapy regimen (50.0% versus 22.2%). Hyponatremic CRS patients showed a trend for a higher in-hospital mortality (15.6% versus 7.6%, p=0.054), but no difference in the one-year mortality (43.3% versus 40.1%, p=0.692). Conclusions All CRS patients showed a high prevalence of diabetes mellitus and a high one-year mortality. In comparison to non-hyponatremic CRS patients, hyponatremic ones were more likely to have hypovolemia, and had a higher likelihood to initiate a temporary, rather than chronic new renal replacement therapy.

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

Cited by 19 publications

References 56 publications

Endogenous Opsin 3 (OPN3) Protein Expression in the Adult Brain Using a Novel OPN3-mCherry Knock-In Mouse Model

Endogenous Opsin 3 (OPN3) Protein Expression in the Adult Brain Using a Novel OPN3-mCherry Knock-In Mouse Model

Diabetes prevalence and outcomes in hospitalized cardiorenal-syndrome patients with and without hyponatremia

High prevalence of diabetes mellitus in hospitalized cardiorenal-syndrome patients with and without hyponatremia.

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