Integrative Physiology
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/29932
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Browsing Integrative Physiology by Author "Balapattabi, Kirthikaa"
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Item Role of Estrogen Receptors in a Model of Dilutional Hyponatremia(2020) Balapattabi, Kirthikaa; Little, Joel; Cunningham, J. Thomas; Nguyen, John-Bosco; Brock, Courtney; Nguyen, DiannaPurpose: Hyponatremia is the most frequently occurring electrolyte disorder and independent risk factor for increased patient mortality. Dilutional hyponatremia in liver failure due to inappropriate arginine vasopressin (AVP) release can be studied using rodent bile-duct ligation (BDL) model. Our previous sex differences studies in BDL rats show compared to males, female and ovariectomized (OVX) BDL rats did not develop hyponatremia, AVP neuron activation, or increased plasma copeptin (CPP; a marker for AVP), compared to sham ligated females. Due to increased adrenal and circulating estradiol (E2) in OVX BDL rats, the role of E2 was unclear. Intracerebroventricular infusion of estrogen receptor (ER) antagonist, ICI 182,780 (ICI) in female BDL rats increased CPP concentration compared to controls. These data suggest ER involvement in prevention of hyponatremia in female BDL rats. However, ICI is also a G protein-coupled estrogen receptor 1 (GPER) agonist. We tested GPER expression within hypothalamo-neurohypophyseal system of female rats. Methods: Immunohistochemistry was performed on three separate sets of forebrain sections from adult female Sprague-Dawley rats. All sets processed for GPER, and the separate sets stained for either AVP, oxytocin (OXY), or glia fibrillary acidic protein (GFAP). Results: Co-localization of GPER+AVP and GPER+OXY was observed in neurohypophyseal neurons (GPER+AVP, 64.8% and GPER+OXY, 64.0%). GPER+GFAP co-localization was not observed. Conclusion: GPER is expressed on subset of AVP and OXY neurons and not astrocytes in hypothalamo-neurohypophyseal system of female rats. Future studies in BDL rats will provide further insight about sex differences in neurohypophyseal function.Item The Effect of Sex on GABAA Receptor Activation on Vasopressin Neurons from the Supraoptic Nucleus(2020) Little, Joel; Cunningham, J. Thomas; Farmer, George; Bachelor, Martha; Balapattabi, Kirthikaa; Brock, CourtneyArginine Vasopressin (AVP), a hormone produced by the magnocellular neurosecretory cells (MNC) of the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus regulates fluid balance and plasma osmolality in healthy individuals. During congestive heart failure (CHF) and liver failure, however, AVP becomes dysregulated leading to increased renal water reabsorption and consequently persistent hyponatremia. Previous work done in the laboratory suggests that female rats may be protected from such dysregulation, perhaps by hormones such as estrogen. Our hypothesis is that under normal physiological conditions, activation of the GABAA receptor inhibits vasopressin neurons within the SON by causing chloride influx, but that under pathophyisiological conditions, activation of the GABAA receptor induces chloride efflux thereby causing activation of the vasopressin neurons in males. It is not known if AVP neurons from female rats behave in a similar manner to AVP neurons from males or are influenced by the estrous cycle. To test our hypothesis, the SON of adult, intact Sprague Dawley rats of both sexes were bilaterally injected with the ClophensorN virus which is a genetically modified virus used to detect Chloride flux in vasopressin neurons using fluorescence. Dissociated neurons from the SON were tested to assess chloride flux in response to the GABAA receptor agonist muscimol. Results show that under normal physiological conditions, muscimol induces Chloride influx in both males and females. Future experiments will assess the effect of GABAA activation in pathophysiological conditions by using the bile-duct ligation model of liver failure.