Mechanical unloading with microgravity exposure during spaceflight induces bone loss in weight bearing bones. Combined with loss of bone due to aging, this disuse bone loss puts astronauts at increased risk of fracture upon returning to 1G conditions. It is important to study countermeasures, such as exercise, to mitigate or prevent this bone loss. This study utilized the hindlimb unloaded (HU) rat model to characterize the effects of resistance exercise on recovery dynamics in-between two bouts of HU. In the larger project adult male Sprague-Dawley rats, six months of age, were divided into the following groups: baseline (sacrificed at 6 months of age); aging cage controls (did not undergo any treatment, sacrificed at 7, 8, 9, 10, and 12 months of age); 1HU7 (one month of HU at 6 months of age followed by three months of ambulatory recovery); 2HU10 (one month of HU at 6 months of age, ambulatory recovery for two months, one month HU at 9 months of age, and final two month ambulatory recovery); 1HU10 (one month HU at 9 months of age and two month ambulatory recovery); and 2HU+Ex (One month HU at 6 months of age, two month resistance exercise recovery, and a 2nd bout of HU at 9 months of age). This thesis focused on the 2HU+Ex data, while utilizing data from other groups for comparisons. The data in this thesis includes ex vivo densitometric and biomechanical properties at the femoral neck (FN), femur midshaft diaphysis (FD), and distal femur metaphysis (DFM). All compartments of BMC increased following exercise recovery above AC at the FN and DFM. Ambulatory recovery values revealed incomplete recovery in total and cortical BMC at the DFM and full recovery in other parameters. DFM and FD vBMD data indicated there were further benefits of exercise during recovery. Geometric data revealed periosteal apposition at the DFM and FN following exercise recovery. FD mechanical properties did not produce benefits of exercise. However, FN maximum force increased above all other groups after exercise recovery. Elastic modulus of the DFM showed benefits of exercise recovery in the response to the 2nd HU.

Psychopharmacological studies have implicated the mesolimbic dopamine (DA) system in the mediation of cost/benefit evaluations about effort-related costs associated with larger rewards. However, the role of DA in risk-based decision making remains relatively unexplored. The present study investigated how systemic manipulations of DA transmission affect risky choice assessed with a probabilistic discounting task. Over discrete trials, rats between two levers; a press on the “small/certain” lever always delivered one reward pellet, whereas a press on the other, “large/risky” lever delivered four pellets, but the probability of receiving reward decreased across the four trial blocks (100%, 50%, 25%, 12.5%). In separate groups of well-trained rats we assessed the effects of the DA releaser amphetamine, as well as receptor selective agonists and antagonists. Amphetamine consistently increased preference for the large/risky lever; an effect that was blocked or attenuated by co-administration of either D₁ (SCH23390) or D₂ (eticlopride) receptors antagonists. Blockade of either of these receptors alone induced risk aversion. Conversely, stimulation of D₁ (SKF81297) or D₂ (bromocriptine) receptors also increased risky choice. In contrast, activation of D₃ receptors with PD128,907 induced risk aversion. Likewise, D₃ antagonism with nafadotride potentiated the amphetamine-induced increase in risky choice. Blockade or stimulation of D₄ receptors did not reliably alter patterns of choice. These findings indicate that DA plays a critical role in mediating risk-based decision making, where increased activation of D₁ and D₂ receptors biases choice towards larger, probabilistic rewards, whereas D₃ receptors appear to exert opposing effects on this form of decision making.

This study used vital bone markers to investigate mineralized tissue adaptation in the periodontium of rats after a hypothermic insult to their maxillary first molars. This hypothermic insult has been shown in previous studies to induce aseptic root resorption with variable effects on ankylosis. A secondary objective was to assess the pulpal changes that occurred concurrent with the changes in the periodontium. Four groups of 7, eight-week old male Sprague Dawley rats were assigned to be euthanased at the day 7, 14, 21 and 28 observation periods. At day 0, 4 groups of 6 rats were subject to a single 20 minute application of dry ice on their maxillary right first molar. The remaining 1 rat within each group did not receive the dry ice. All rats were given 2 sequential bone labels, calcein 5mg/kg and alizarin red 30mg/kg, administered intraperitoneally 8 days apart. The timing of the labels was such that all rats were euthanased 2 days after the last label. The rat maxillae were fixed in ethanol and embedded undecalcified in methylmethacrylate. Ten micrometre coronal sections were obtained through the furcation of the first molars with three of each group of ten consecutive sections being unstained, stained with von Kossa/ hematoxylin and eosin counterstain, or decalcified and stained with hematoxylin and eosin, respectively. Unstained sections were viewed under fluorescence, while transmitted light microscopy was used for the other sections. Mineral apposition rates along the bone, root and pulpal surfaces as well as periodontal ligament width were measured using histomorphometry. Semiquantitative measurements of the resorptive surfaces within the periodontium were also noted. Multivariate and negative binomial regression statistical analyses were used to identify influencing variables. A focal pattern of ankylosis was observed at days 14 and 21 in 3 rats and was not seen at day 28. In both the treated and control teeth, appositional activity was greatest along bone and least along the root surface. Mineral tissue apposition rates along the bone and root surface displayed an initial spike during day 14 but declined to levels of the control teeth by day 28. A longer time lag was observed with appositional activity in the pulp which also displayed a declining trend towards the control teeth values by day 28. Resorption levels along the root surface continued to remain significantly (p<0.0001) elevated. The significantly (p<0.0001) wider periodontal ligament width in the treated molars showed a declining trend towards that of the control teeth by day 28. There was a temporary disturbance of mineralized tissue adaptation on the bone and root surfaces with a recovery of cellular vitality within the periodontium and pulp and a trend towards homeostasis of the periodontal ligament width. The null hypotheses that a single prolonged thermal insult on a rat has no effect on mineralized tissue adaptation within the periodontium and pulp chamber and that the periodontal ligament width within the interradicular region does not change in response to thermal trauma induced by the present study were rejected. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1345386 / Thesis (D.Clin.Dent) - University of Adelaide, School of Dentistry, 2008

Texte remanié de: "Habilitation à diriger des recherches, Histoire, Bordeaux 3, 2005" / Bibliogr. p. 329-387. Notes bibliogr. Index. Version étoffée d'un texte présenté en décembre 2005 (pour l'obtention de l'habilitation à diriger des recherches).

Proefschrift Maastricht. / Met lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Maastricht. / Auteursnaam op omslag: Mat Daemen. Met lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Maastricht. / Lit.opg. - Met samenvatting in het Nederlands.

Proefschrift Maastricht Rijksuniversiteit Limburg. / Lit. opg.: p. 161-173. - Met samenvatting in het Nederlands.

Proefschrift Maastricht. / Auteurnaam op omslag: Jan J.G.M. Verschuuren. Ondertitel op omslag: antibodies, idiotypes and anti-idiotypes. Met lit. opg. - Met een samenvatting in het Nederlands.

Proefschrift Maastricht. / Met lit. opg. - Met samenvatting in het Nederlands.