ANG II receptor subtype 1a gene knockdown in the subfornical organ prevents increased drinking behavior in bile duct-ligated rats

Walch, Joseph D.; Nedungadi, T. Prashant; Cunningham, J. Thomas

doi:10.1152/ajpregu.00163.2014

Cited by 12 publications

(10 citation statements)

References 74 publications

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“…ΔCt was measured by calculating the difference between the S18 and the corresponding gene of interest Ct values. For obtaining the ΔΔCt value, this value was then subtracted from the difference between the average of control S18 and control gene of interest Ct values [22,28,31,34].…”

Section: Laser Capture Microdissection and Quantitative Real-time Pcrmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor and Supraoptic Vasopressin Neurons in Hyponatremia

Balapattabi¹,

Little²,

Bachelor³

et al. 2019

Neuroendocrinology

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Hyponatremia due to elevated arginine vasopressin (AVP) secretion increases mortality in liver failure patients. The mechanisms causing dysregulation of AVP secretion are unknown. Our hypothesis is that inappropriate AVP release associated with liver failure is due to increased brain-derived neurotrophic factor (BDNF) in the supraoptic nucleus (SON). BDNF diminishes GABA A inhibition in SON AVP neurons by increasing intracellular chloride through tyrosine receptor kinase B (TrkB) activation and downregulation of K+/Cl-cotransporter 2 (KCC2). This loss of inhibition could increase AVP secretion. This hypothesis was tested using shRNA against BDNF (shBDNF) in the SON in bile duct ligated (BDL) male rats. All BDL rats had significantly increased liver weight (p < 0.05; 6-9) compared to shams. BDL rats with control shRNA injections (BDL scrambled [SCR]) developed hyponatremia with increased plasma AVP and copeptin (CPP; all p < 0.05; 6-9) compared to sham groups. This is the first study to show that phosphorylation of TrkB is significantly increased along with significant decrease in phosphorylation of KCC2 in BDL SCR rats compared to the sham rats (p < 0.05; 6-8). Knockdown of BDNF in the SON of BDL rats (BDL shBDNF) significantly increased plasma osmolality and hematocrit compared to BDL SCR rats (p < 0.05; 6-9). The BDL shBDNF rats had significant (p < 0.05; 6-9) decreases in plasma AVP and CPP concentration compared to BDL SCR rats. The BDNF knockdown also significantly blocked the increase in TrkB phosphorylation and decrease in KCC2 phosphorylation (p < 0.05; 6-8). The results indicate that BDNF produced in the SON contributes to increased AVP secretion and hyponatremia during liver failure.

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Section: Laser Capture Microdissection and Quantitative Real-time Pcrmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor and Supraoptic Vasopressin Neurons in Hyponatremia

Balapattabi¹,

Little²,

Bachelor³

et al. 2019

Neuroendocrinology

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“…LCM has been used by other labs to profile the molecular composition of various hypothalamic regions (Tables 1–3). For example, to highlight a few studies by way of illustration, LCM has been used to confirm: 1) the effectiveness of adeno-associated viral knockdown of angiotensin II receptor subtype 1a in the subfornical organ (SFO) of rat brain [449]; 2) reductions in gene expression in brains of steroidogenic factor 1 (SF-1) in the VMH of knock-out mice [339]; and 3) fasting-elicited changes in gene expression in the PVH and the impact of leptin replacement on these genes [440]. …”

Section: Laser-capture Microdissection Studies: Methodological Considmentioning

confidence: 99%

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

Khan

Grant

Martínez

et al. 2018

Advances in Neurobiology

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“…; Walch et al. ; Saxena et al. ) based on our previous study that showed ACE1 staining in the MnPO is not found in astrocytes and is mainly in neurons (Faulk et al.…”

Section: Introductionmentioning

confidence: 95%

Angiotensin converting enzyme 1 in the median preoptic nucleus contributes to chronic intermittent hypoxia hypertension

2017

Self Cite

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Obstructive sleep apnea is associated with hypertension and cardiovascular disease. Chronic intermittent hypoxia is used to model the arterial hypoxemia seen in sleep apnea patients and is associated with increased sympathetic nerve activity and a sustained diurnal increase in blood pressure. The renin angiotensin system has been associated with hypertension seen in chronic intermittent hypoxia. Angiotensin converting enzyme 1, which cleaves angiotensin I to the active counterpart angiotensin II, is present within the central nervous system and has been shown to be regulated by AP‐1 transcription factors, such as ΔFosB. Our previous study suggested that this transcriptional regulation in the median preoptic nucleus contributes to the sustained blood pressure seen following chronic intermittent hypoxia. Viral mediated delivery of a short hairpin RNA against angiotensin converting enzyme 1 in the median preoptic nucleus was used along with radio‐telemetry measurements of blood pressure to test this hypothesis. FosB immunohistochemistry was utilized in order to assess the effects of angiotensin converting enzyme 1 knockdown on the activity of nuclei downstream from median preoptic nucleus. Angiotensin converting enzyme 1 knockdown within median preoptic nucleus significantly attenuated the sustained hypertension seen in chronic intermittent hypoxia. Angiotensin converting enzyme 1 seems to be partly responsible for regulating downstream regions involved in sympathetic and blood pressure control, such as the paraventricular nucleus and the rostral ventrolateral medulla. The data suggest that angiotensin converting enzyme 1 within median preoptic nucleus plays a critical role in the sustained hypertension seen in chronic intermittent hypoxia.

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ANG II receptor subtype 1a gene knockdown in the subfornical organ prevents increased drinking behavior in bile duct-ligated rats

Cited by 12 publications

References 74 publications

Brain-Derived Neurotrophic Factor and Supraoptic Vasopressin Neurons in Hyponatremia

Brain-Derived Neurotrophic Factor and Supraoptic Vasopressin Neurons in Hyponatremia

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

Angiotensin converting enzyme 1 in the median preoptic nucleus contributes to chronic intermittent hypoxia hypertension

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