ABSTRACT
It is well documented that estrogens inhibit fluid intake. Most of this research, however, has focused on fluid intake in response to dipsogenic hormone and/or drug treatments in euhydrated rats. Additional research is needed to fully characterize the fluid intake effects of estradiol in response to true hypovolemia. As such, the goals of this series of experiments were to provide a detailed analysis of water intake in response to water deprivation in ovariectomized female rats treated with estradiol. In addition, these experiments also tested if activation of estrogen receptor alpha is sufficient to reduce water intake stimulated by water deprivation and tested for a role of glucagon like peptide-1 in the estrogenic control of water intake. As expected, estradiol reduced water intake in response to 24 and 48 h of water deprivation. The reduction in water intake was associated with a reduction in drinking burst number, with no change in drinking burst size. Pharmacological activation of estrogen receptor alpha reduced intake. Finally, estradiol-treatment caused a leftward shift in the behavioral dose response curve of exendin-4, the glucagon like peptide-1 agonist. While the highest dose of exendin-4 reduced 10 min intake in both oil and estradiol-treated rats, the intermediate dose only reduced intake in rats treated with estradiol. Together, this series of experiments extends previous research by providing a more thorough behavioral analysis of the anti-dipsogenic effect of estradiol in dehydrated rats, in addition to identifying the glucagon like peptide-1 system as a potential bioregulator involved in the underlying mechanisms by which estradiol reduces water intake in the female rat.
Subject(s)
Drinking , Glucagon-Like Peptide 1 , Animals , Female , Rats , Dehydration , Drinking/drug effects , Estradiol/pharmacology , Estrogen Receptor alpha , Exenatide/pharmacology , Glucagon-Like Peptide 1/pharmacology , Transcription FactorsABSTRACT
The inhibitory effect of estradiol (E2) on water intake has been recognized for 50 years. Despite a rich literature describing this phenomenon, we report here a previously unidentified dipsogenic effect of E2 during states of low fluid intake. Our initial goal was to test the hypothesis that the anti-dipsogenic effect of E2 on unstimulated water intake is independent of its anorexigenic effect in female rats. In support of this hypothesis, water intake was reduced during estrus, compared to diestrus, when food was present or absent. Water intake was reduced by E2 in ovariectomized rats when food was available, demonstrating a causative role of E2. Surprisingly, however, when food was removed, resulting in a significant reduction in baseline water intake, E2 enhanced drinking. Accordingly, we next tested the effect of E2 on water intake after an acute suppression of intake induced by exendin-4. The initial rebound drinking was greater in E2-treated, compared to Oil-treated, rats. Finally, to reconcile conflicting reports regarding the effect of ovariectomy on water intake, we measured daily water and food intake, and body weight in ovariectomized and sham-operated rats. Predictably, ovariectomy significantly increased food intake and body weight, but only transiently increased water intake. Together these results provide further support for independent effects of E2 on the controls of water and food intake. More importantly, this report of bidirectional effects of E2 on water intake may lead to a paradigm shift, as it challenges the prevailing view that E2 effects on fluid intake are exclusively inhibitory.
Subject(s)
Drinking , Estradiol , Animals , Body Weight , Eating , Estradiol/pharmacology , Estrogens , Female , Humans , Ovariectomy , RatsABSTRACT
Diabetic peripheral neuropathy (DPN) is estimated to affect 50% of diabetic patients. Although DPN is highly prevalent, molecular mechanisms remain unknown and treatment is limited to pain relief and glycemic control. We provide a novel model of acute DPN in zebrafish ( Danio rerio) larvae. Beginning 5 days postfertilization (dpf), zebrafish expressing nitroreductase in their pancreatic ß-cells were treated with metronidazole (MTZ) for 48 h and checked for ß-cell ablation 7 dpf. In experimental design, this was meant to serve as proof of concept that ß-cell ablation and hyperglycemia are possible at this time point, but we were surprised to find changes in both sensory and motor nerve components. Compared with controls, neurod+ sensory neurons were often observed outside the dorsal root ganglia in MTZ-treated fish. Fewer motor nerves were properly ensheathed by nkx2.2a+ perineurial cells, and tight junctions were disrupted along the motor nerve in MTZ-treated fish compared with controls. Not surprisingly, the motor axons of the MTZ-treated group were defasciculated compared with the control group, myelination was attenuated, and there was a subtle difference in Schwann cell number between the MTZ-treated and control group. All structural changes occurred in the absence of behavioral changes in the larvae at this time point, suggesting that peripheral nerves are influenced by acute hyperglycemia before becoming symptomatic. Moving forward, this novel animal model of DPN will allow us to access the molecular mechanisms associated with the acute changes in the hyperglycemic peripheral nervous system, which may help direct therapeutic approaches.
Subject(s)
Hyperglycemia/physiopathology , Insulin-Secreting Cells/metabolism , Nitroreductases/metabolism , Peripheral Nervous System/physiopathology , Animals , Animals, Genetically Modified , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Behavior, Animal/drug effects , Cell Count , Ganglia, Spinal/cytology , Ganglia, Spinal/metabolism , Homeobox Protein Nkx-2.2 , Homeodomain Proteins , Hyperglycemia/chemically induced , Hyperglycemia/psychology , Larva , Metronidazole/pharmacology , Motor Neurons/drug effects , Motor Neurons/metabolism , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Nitroreductases/antagonists & inhibitors , Peripheral Nervous System/cytology , Schwann Cells/drug effects , Sensory Receptor Cells/metabolism , Zebrafish , Zebrafish ProteinsABSTRACT
This study examines the mechanisms through which workaholism and work engagement impact work-home conflict and enrichment, respectively. Specifically, we examine the mediating role of positive and negative emotions (e.g. joviality and guilt) in the relationship between workaholism, work engagement and work-home outcomes. Results, based on a sample of 340 working adults participating in a two-wave study, indicate that negative emotions-particularly anxiety, anger and disappointment-mediate the relationship between workaholism and work-home conflict and positive emotions-particularly joviality and self-assurance-mediate the relationship between work engagement and work-home enrichment. These results provide further evidence that workaholism and work engagement are related to distinct sets of emotional variables and disparate work and home outcomes.