Integrative Physiology
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/29932
Browse
Browsing Integrative Physiology by Author "Cunningham, J. Thomas"
Now showing 1 - 3 of 3
- Results Per Page
- Sort Options
Item Role of A1/A2 Neurons in Increased Vasopressin Release in Male Bile Duct Ligated Rats(2020) Little, Joel; Cunningham, J. Thomas; Aikins, AtoBile duct ligation (BDL), a rat model of liver failure causes increased vasopressin release leading to water retention and a decrease in plasma osmolality. Water retained in ascites leads to a perceived decrease in plasma volume by the A1/A2 norepinephrine neurons in the caudal ventrolateral medulla (CVLM) and the nucleus tractus solitarius (NTS) respectively, increasing vasopressin release. We hypothesized that lesioning norepinephrine A1/A2 neurons will prevent increased plasma vasopressin (measured as a function of plasma copeptin concentrations), normalize hematocrit and plasma osmolality, and decrease the number of immunoreactive ΔFosB and DβH cells in the NTS and CVLM. To investigate the role of A1/A2 neurons in the increase in vasopressin release observed in male BDL rats, anti-DβH-Saporin [IT-03] (Advanced Targeting Systems), or vehicle was injected into the SON. BDL surgery or sham surgery was performed after two weeks. Four weeks following the BDL/Sham surgery, the rats were sacrificed, and blood samples were taken for copeptin, hematocrit and plasma osmolality measurements. Hindbrains were processed for immunohistochemistry. The results showed a significant decrease in CVLM ΔFosB reactive cells in the Saporin/BDL group (n=2) as compared to the Vehicle/BDL group (n=3) (p< 0.001). DβH immunoreactive cells in both the CVLM and NTS were significantly decreased in the Saporin/BDL group as compared to the vehicle/BDL group (p< 0.001). However, differences were not observed for the copeptin concentration, hematocrit and plasma osmolality. The results suggest that lesions of SON-projecting A1/A2 neurons may not be sufficient to prevent vasopressin release associated with BDL.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.