Browsing by Subject "rat"
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Item Characterization of the Bone Loss and Recovery Response at the Distal Femur Metaphysis of the Adult Male Hindlimb Unloaded Rat(2012-02-14) Davis, Joshua MorganExtended periods of mechanical unloading are known to be detrimental to bone health. Astronauts who spend months in microgravity aboard the International Space Station (ISS) are at particular risk. It is anticipated that NASA will not drastically increase the size of the astronaut corps, and this will mean increased likelihood of repeat missions for more astronauts. Thus, it is important to better understand the effects that prolonged, multiple bouts of unloading have on bone. This study utilized the hindlimb unloaded (HU) rat model to examine bone loss and recovery for single and double unloading bouts. Adult male Sprague-Dawley rats (6 months old) were randomized into the following groups: baseline (sacrificed at 6 months), 1HU7 (unloaded for 1 month, weight-bearing recovery for 3 months), 2HU10 (unloaded for 1 month, recovered for 2 months, unloaded for another month, and then recovered 2 months), 1HU10 (normal cage activity until 1 month HU ending at month 10, 2 month recovery followed), and aging controls (remained ambulatory throughout experiment). Every month (28 days), animals were terminated and the left femurs were excised, resulting in n=15 per group for each time point. Mineral and geometric properties were measured using peripheral quantitative computed tomography (pQCT) at the distal femur metaphysis, and quasi-static reduced platen compression (RPC) was used to estimate the mechanical properties of cancellous bone. Strength indices based on pQCT parameters were calculated as predictors of mechanical properties. Bone mass properties decreased due to HU and recovered within 2-3 months post-HU. A combination of increased periosteal apposition and endocortical resorption also occurred during HU. The initial HU bout suppressed normal age-related increases in mechanical properties and recovered within 1-2 months. Cancellous compressive strength index (CSI) most closely matched changes in mechanical properties. A second HU bout after two months recovery had a less detrimental effect on pQCT parameters but a greater negative impact on mechanical properties, when compared to pre-HU values. The opposite is true for mechanical properties if loss is characterized relative to aging controls. Recovery after the second HU period did not appear to be significantly affected by a previous bout of HU.Item Constrictor prostanoid-potentiated vascular contraction: regulation of endothelial and vascular smooth muscle mechanism by estrogen(Texas A&M University, 2004-09-30) Li, MinThe objectives of this research were to elucidate the involvement of constrictor prostanoids in the vascular reactivity to vasopressin (VP) and the role of estrogen in the regulation of the constrictor prostanoid mechanism in the female rat. Aortas obtained from male, intact (InT)-, ovariectomized (OvX)- and OvX + estrogen-replaced (OvX+Est)-female rats were studied. Contractile responses to VP were examined in the presence of nonselective and selective cyclooxygenase (COX) inhibitors. Basal and VP-stimulated release of thromboxane A2 (TxA2) and prostacyclin (PGI2) from the aortic wall were measured. Concentration-response curves to exogenous TxA2 were also obtained. To elucidate the regulatory effects of estrogen on the constrictor prostanoid pathway, the expression of COX-1, COX-2, thromboxane synthase (TxS) and thromboxane receptor (TP) mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR). Further, immunohistochemistry was employed to determine COX-1, COX-2 and TxS protein expression in aortic endothelium and vascular smooth muscle. The major findings of this research are that: 1) The contractile responses of the female rat aorta to VP were enhanced by COX-2-mediated production of constrictor prostanoids (PGH2/TxA2), and this mechanism is potentiated by estrogen; 2) Vascular reactivity to exogenous TxA2 was higher in the female than in the male rat aorta, and OvX attenuated and estrogen replacement therapy restored vascular reactivity to TxA2 in the female aorta; 3) VP-stimulated release of endogenous TxA2 and PGI2 were higher in the female than in the male rat aorta, and OvX attenuated and estrogen replacement therapy restored VP-stimulated release of these endogenous prostanoids by the female aorta; and 4) The expression of COX-2 and TxS mRNA and protein, and the expression of TP mRNA were higher in InT-female than in male, and were reduced by OvX and restored by estrogen replacement therapy. In conclusion, estrogen potentiated contractile responses of the female rat aorta to VP by upregulating the expression of COX-2, TxS and TP; thereby enhancing VP-induced release of TxA2, as well as the vascular reactivity to endogenous TxA2.Item D2 Dopamine Receptor Mediation of Risky Decision-making(2011-08-08) Simon, Nicholas WayneExcessive risk-taking is a characteristic of several psychopathological disorders. In order to alleviate maladaptive risky behavior, a thorough understanding of the neurobiological and pharmacological substrates of risky choice must be developed. In this dissertation, the ?risky decision-making task? was utilized to explore the mechanisms by which dopamine mediates risky choice. In experiment 1, we characterized rats in risky decision-making as well as a variety of other behavioral traits. This was performed to determine if the behavioral patterns obtained in the risky decision-making task represent an independent cognitive construct rather than a function of a separate behavioral trait. Risky decision-making performance was not correlated with measures of motivation, anxiety, pain tolerance, or other types of decision-making. In contrast, risky choice was correlated with impulsive action as assessed by the Differential Rates of Low Responding Task, suggesting that risky choice may be mechanistically similar to impulsive action. In experiment 2, the effects of various dopaminergic drugs on risky decision-making was investigated. Amphetamine administration attenuated risky choice, while the dopamine antagonist ?-flupenthixol had no effect on risky choice. Agonists and antagonists specific to D1 dopamine receptors had no effects on risky choice; however, the D2 dopamine receptor agonist bromocriptine reduced risky choice in a manner similar to amphetamine. Furthermore, coadministration of amphetamine with a D2 antagonist abolished amphetamine?s effects on risky choice, and amphetamine?s effects were unaffected by coadministration of a D1 antagonist. These data suggest that D2 signaling at the receptor is particularly critical to risky decision-making behavior. In experiment 3, D2 dopamine receptor mRNA abundance was assessed in rats that had been previously characterized in risky decision-making using in situ hybridization. Levels of D2 cRNA hybridization in both orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC) predicted risky decision-making behavior as assessed by nonlinear curve estimation analyses. Interestingly, opposite relationships between D2 mRNA abundance and risky choice were observed in these two cortical areas, with OFC D2 mRNA abundance showing a U-shaped relationship with risky choice, and mPFC D2 mRNA resembling an inverted U-curve. Additionally, increased levels of D2 mRNA in dorsal striatum were observed in risk-averse rats in comparison to risk-taking rats. In conclusion, these data suggest that signaling via D2 dopamine receptors is an important mediator of risky decision-making behavior, and that D2 signaling in frontostriatal circuitry may be particularly relevant toward these behaviors.Item Methods for reduced platen compression (RPC) test specimen cutting locations using micro-CT and planar radiographs(Texas A&M University, 2004-09-30) Lemmon, HeberThis study looks at improving reduced platen compression (RPC) specimen preparation procedures by developing a better method for locating the ideal RPC specimen on each bone. These improvements are aimed at decreasing the amount of time required to complete an RPC analysis and improving the quality of the obtained results. High-resolution micro-CT scans are used to gain a better understanding of rat long bone anatomy by quantifying the location, shape, and orientation of the growth plate, primary spongiosa, and secondary spongiosa. Micro-CT analysis shows that there are easily identifiable external landmarks on the anterior side of both tibias and femurs that identify the end of the growth plate and the point at which the top of an ideal RPC specimen should be located. The landmarks are the most proximal tip of the patellar surface for the femur and the base of the tibial tuberosity for the tibia. This study also analyzes the effect of variations in the actual RPC specimen location from the ideal location and the effect of different platen sizes on test results using BMD as a surrogate for mechanical properties. The analysis shows that the BMD increases as the target RPC specimen location approaches the growth plate and decreases on moving away from the growth plate. The study also indicates that consistency is necessary when obtaining RPC specimens to avoid error due to variation from the specified landmark. Additionally, the BMD decreased as the diameter of the platen is reduced. Choosing platen size then becomes a trade off between testing the greatest amount of cancellous bone possible and potentially higher load sharing by the cortical shell with larger platen sizes as well as the risk of compressing cortical bone during the test.Item Osteogenic effect of electric muscle stimulation as a countermeasure during hindlimb unloading(Texas A&M University, 2007-09-17) Alcorn, Justin DowRats that undergo hindlimb unloading (HU) as a simulation for space flight experience bone changes similar to astronauts in microgravity. The purpose of this research was to assess whether an exercise countermeasure would be effective in preventing or mitigating bone degradation during HU. Controlled electrical muscle stimulation was applied to the lower left hindlimb to simulate resistive exercise. Adult 6-mo. old male rats were assigned to 3 groups of 12 each: hindlimb unloaded (HU), aging cage control (CC), and baseline (BL). The CC group was pair-fed to match the nutritional intake of HU animals during the 28 days of the study. The left leg was exercised 3 days a week for the duration of the study, with the unexercised right leg serving as a contra-lateral control. Mechanical tests were conducted to assess the strength of cancellous bone in the proximal tibia metaphysis. Although isolated specimens of cancellous bone are not feasible, reduced platen compression (RPC) was employed to directly load only the cancellous core region of each specimen. There was no significant difference in ultimate stress or elastic modulus between BL, CC, and HU-Ex (exercised). However, HU-Ex results were dramatically and significantly higher than HU-No Ex (contra-lateral unexercised control) for both ultimate stress (68%) and elastic modulus (81%). It is also notable that ultimate stress was 32% higher (but not statistically significant) for HU-Ex compared to CC. The total bone mineral density in the tibial metaphysis was significantly larger, 11%, in the HUEx compared to the HU-No Ex group's values. The results clearly demonstrate the efficacy of the exercise protocol in preventing the substantial mechanical deterioration induced by HU.Item Reversible Inactivation of the Bed Nucleus of the Stria Terminalis Blocks Reinstatement But Not Renewal of Extinguished Fear(2014-12-08) Kim, Janice JThe bed nucleus of the stria terminalis (BNST) is thought to be involved in the expression of fear to shock-associated contexts, but not to discrete conditional stimuli (CSs) paired with shock. Because context plays an important role in the extinction and relapse of fear, we sought to examine the contribution of the BNST to two different relapse phenomena: renewal and reinstatement. In the renewal experiment, male Long-Evans rats received 5 tone-shock trials for conditioning in ?context A?; 24 hours later they received 45 tone?alone (extinction) trials in either ?context B? or ?context C?. Ten minutes prior to a retrieval test (5 tone-alone trials), rats were infused with either selective agonist for GABAA receptors, muscimol or vehicle in the BNST. In the reinstatement experiment, rats underwent a similar procedure, but were presented with an unsignaled ?reminder? shock in the extinction context to reinstate fear. As before, we examined the influence of muscimol inactivation of the BNST during a retrieval testing 24-hours after the reinstatement shock. In the reinstatement test, rats with muscimol infusion showed significantly less freezing than did rats with vehicle infusion. In contrast, BNST inactivation did not attenuate the renewal of fear to an extinguished CS outside the extinction context. These data indicate that the BNST is involved in forms of fear relapse that depend on direct associations of the test context with an aversive US.Item The role of constrictor prostanoids in the development of aortic coarctation-induced hypertension in male and female rats(Texas A&M University, 2005-02-17) Baltzer, Wendy IreneVascular reactivity to vasopressin and phenylephrine is potentiated by constrictor prostanoids (CP) in normotensive female (F) but not male (M) rat aorta and CP function is estrogen-dependent. This study investigated the effects of estrogen on CP function and arterial blood pressure (MAP) during development of aortic coarctation-induced hypertension (HT). M and F rats, (15-18 wks.) in four groups: normotensive (NT), hypertensive (HT), ovariectomized (OVX), and OVX estrogen-replaced (OE), underwent abdominal aortic coarctation or sham surgery (NT). At 14 days, SQ 29,548 (SQ, Thromboxane A2 (TXA2) receptor antagonist) was given i.v. to the groups. In another experiment, rats received Ridogrel (TXA2 receptor antagonist+TXA2 synthase (TXS) inhibitor) or vehicle (methyl cellulose) daily, for 14 days. Thoracic aortae were analyzed for morphology, incubated in Kreb?s Henseleit Buffer (KHB) ? angiotensin II (ANG II), or underwent continuous pulsatile flow and pressure experiments (PFP) with KHB ? ANG II. Perfusate was analyzed for thromboxane B2 (TXB2) and prostaglandin F1α (PGF1α). RT-PCR and immunohistochemistry were performed for TXS. MAP was higher in F-HT than in M-HT after 14 days. SQ infusion reduced MAP substantially more in F-HT and OE-HT than in others. Ridogrel prevented increases in MAP in F/OE-HT rats, but not M/OVX-HT. Basal release of TXB2 and PGF1α increased to a greater extent in F-HT than in M-HT relative to their controls. ANG II-stimulated TXB2 and PGF1α release increased to a greater extent in F-HT than in M-HT. With or without ANG II, TXB2 production in HT during PFP increased with estrogen. PGF1α increased during PFP with estrogen, however not with ANG II. Pressurization resulted in less diameter change in F and OE-HT than in OVX-HT. Elastin increased with HT (inhibited by Ridogrel) in all but M. Collagen increased in HT with estrogen (inhibited by Ridogrel). Neither OVX-HT nor Ridogrel had any effect on morphology. Estrogen increased TXS with HT. Estrogen enhanced vascular CP and MAP in F-HT by increased expression of TXS and collagen density in the vasculature indicating that in aortic coarctation-induced HT, CP are upregulated by estrogen. Specific forms of HT in human beings may involve estrogen-induced vascular CP upregulation.