Thesis (Ph. D.)--University of California, Riverside, 2010. / Includes abstract. Available via ProQuest Digital Dissertations. Title from first page of PDF file (viewed May 17, 2010). Includes bibliographical references. Also issued in print.

Akademisk avhandling--Copenhagen. / Bibliography: p. 102-109.

Thesis (Ph. D.)--Virginia Commonwealth University, 2005. / Prepared for: Dept. of Pharmacology and Toxicology. Bibliography: leaves 142-153.

Thesis (Ph.D.)--University of Florida, 2004. / Typescript. Title from title page of source document. Document formatted into pages; contains 97 pages. Includes Vita. Includes bibliographical references.

Thesis (M.S.)--Uniformed Services University of the Health Sciences, 2006 / Typescript (photocopy)

Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (leaves 75-84).

L’objectif principal de cette thèse est de comprendre l’origine de la variabilité d’expression du comportement sexuel (CS). Nous avons trouvé que l’approche latérale est le CS le plus exprimé et que sa quantification peut servir comme mesure de la libido et donner une idée de la performance. Nous avons montré des effets remarquables de l’âge et de la lumière sur le CS du bélier. Nous avons également montré que les structures cérébrales impliquées dans la phase motivationnelle et consommatoire ne étaient pas les mêmes et que quel que soit le partenaire sexuel préféré, l’exposition à ce partenaire provoquait une activation des mêmes structures cérébrales ; le niveau de libido semble être déterminé par des sites spécifiques et bien précis comme l’aire préoptique, le noyau paraventriculaire et la partie médiane du Lit de la strie terminale. Le Cortex ent pourrait fonctionner comme un inhibiteur de la motivation hétérosexuelle. / The main objective of this thesis was to acquire a better understanding of the origin of the variability of the expression of sexual behavior. The nudging is most expressed sexual behavior and quantification of this behavior can be used to measure their libido and give a clue on their performance. We have discovered the remarkable effects of age et lighting of the ram's sexual behavior and that the cerebral structures involved in the motivation phase and consummatory phase are not the same and seems that, no matter which sexual partner is chosen, the fact of being exposed to this partner provokes the activation of these cerebral structures et what the expression of sexual motivation level seems to have specific and precise sites in the Preoptic Area, the Paraventricular Nucleus (PVN) and the Nucleus of the bed of the striae terminalis medial (BNSTmed). The Entorhinal cortex could function as an inhibitor of heterosexual motivation.

Genetically based Central Nervous System (CNS) disorders remain a largely unresolved issue in the world today. Our genome is the source of our greatest strengths and weaknesses. For this reason, intelligent modification of the genome's DNA is a profoundly beneficial goal in the maximization of the overall health of the human race. Potential benefit in this field is currently limited in both effectiveness and safety in regards to the delivery of therapeutic genes into the nucleus, which is protected by many evolution-based barriers. Evolution has also favored the development of highly specialized and infectiously effective viruses capable of overcoming such boundaries. By neutering the naturally occurring and pathologically benign Adeno-Associated Virus (AAV) we have transformed what was once a virus, into a "pure" vector, taking full advantage of evolution's diligent enhancement of these genetic hijackers without introducing unacceptable danger to patients. We utilized the logically engineered, castrated form of AAV serotype 9 (recombinant AAV9/rAAV9) to act as a vehicle for two reporter genes, Enhanced Green Fluorescent Protein (EGFP) and Firefly Luciferase (Fluc) with the goal of assessing and improving the efficiency of vector transduction in murine CNS. We found that rAAV9, when infused into the intrathecal space of mice is capable of extensive and intensive transduction of both neurons and astrocytes throughout the entire length of the SC as well as the hind regions of the brain (brainstem and cerebellum). We also found that efficiency of transduction was best in our highest dose groups, 1E+12 genome copies (GC) in Experiment 1 and 2E+12 GC in Experiment 2, both of which received rAAV9 particles via the two commercially available (100μL and the 200μL) ALZET® Osmotic Pump designs. Administering dosage higher than this directly into the intrathecal space was limited by the size of the pump reservoir and rAAV9 production titer. We are currently attempting to achieve a more complete CNS transduction by performing another experiment in which we place the pump cannula directly into the intracerebroventricular (ICV) space of the lateral ventricles. Our findings reveal that infusion of rAAV9 by intrathecal placed pump cannula is more effective than any other method tested in this study int the transduction of neurons and glial cells of adult&ndashmouse CNS. By elucidating a mode of delivery that maximizes the robustness of transduction efficiency, our results are a critical building block in designing a cure for the array of genetic-based diseases of the CNS, which are currently untreatable

La L-Théanine (L-5-N-éthylglutamine) est un acide aminé présent dans le thé vert et qui a une structure similaire à celle de l'acide glutamique, le neurotransmetteur majoritaire du système nerveux central, SNC. La L-théanine possède la capacité de traverser la barrière hémato-encéphalique en plus de ses nombreuses activités physiologiques et pharmacologiques, anxiolytique et relaxante. La théanine et ses dérivés sont donc considérés comme des outils indispensables pour la compréhension de la synapse glutamatergique plus précisément. Nous avons synthétisé la théanine énantiomériquement pure (L et D). Nous avons développé deux nouvelles méthodes de synthèse de la théanine optiquement pure. Ensuite, nous avons décrit la préparation des dérivés 5-N-alkylés de la théanine et les dipeptides -glutamique en tant qu'analogues 5-N-substitués de la théanine. Dans le but d'élargir l'éventail d'applications de la Théanine ayant un intérêt biologique, nous avons synthétisé des dipeptides contenant la Théanine. Nous présentons également un accès aux dérivés 4-arylés de la théanine, via une alkylation régio et stéréosélective de l'acide pyroglutamique jamais décrit dans la littérature. L'analyse rigoureuse des intermédiaires réactionnels et des produits finaux par les RX, la RMN 1H à 600 MHZ et l'HRMS a prouvé l'obtention d'un seul diastéréoisomère (2S, 4R)-4-aryle théanineLes résultats des tests biologiques, utilisant la technique de l'imagerie calcique, montrent que les deux énantiomères L et D de la théanine possède un effet agoniste vis-à-vis les récepteurs NMDA et que cet effet est beaucoup plus important dans le cas de l'énantiomère (D). Parmi les analogues 5-N-alkylés de la théanine ayant un effet agoniste spécifique des récepteurs NMDA, la 5-N-Propyl-Gln (L et D) montre une activité en tant qu'agoniste beaucoup plus importante que la théanine même (naturelle ou synthétique) et aucun effet n'a été observé sur les récepteurs AMPA et métabotropiques. La L-théanine et ses dérivés pourraient donc être des structures intéressantes pour développer de nouveaux outils pharmacologiques nécessaires à l'étude des récepteurs glutamatergiques (métabotropiques et/ ou ionotropiques). / L-Theanine (5-N-L-ethylglutamine) which is an amino acid found in green tea, it has a structure similar to that of glutamic acid. L-theanine has the ability to cross the blood-brain barrier in addition to its physiological and pharmacological activities.Given the importance of this molecule as essential for the investigation of physiological roles of CNS tools, we synthesized the enantiomerically pure theanine (L and D). A serie of 5-N-substituted theanine were also synthesized. In order to broaden the range of applications of theanine, we synthesized dipeptides containing Theanine for the purpose of obtaining products that have biological significance. The regio and stereoselectively synthesized analogs of L-theanine in the 4-position substituted with an aryl group has been developed to be tested at the level of glutamate receptors.The results of biological tests, using calcium imaging technique, show that theanine with its two enantiomers (D and L) has an agonistic effect vis-à-vis the NMDA receptors and that this effect was much greater with the enantiomer (D). Among the 5-N-alkylated analogs of theanine which they had only an agonistic effect on the NMDA receptor, 5-N-Propyl-Gln (L and D) has activity as an agonist much larger than the theanine and no effects were scored on AMPA receptors and metabotropic. L-theanine and its derivatives could be interesting structures to develop new pharmacological tools to study glutamate receptors (metabotropic and / or ionotropic).

Group B Sox genes play a critical developmental role in both vertebrates and insects. Within the model species Drosophila melanogaster, two SoxB genes, Dichaete and SoxNeuro, have been shown to act as ‘master regulators’ in the early development of the central nervous system. SoxB genes have only been characterised in a handful of arthropod species thus far, with most work to date focusing on drosophilids. The purpose of this investigation was twofold. First, I set out to resolve the phylogenetic origins of arthropod SoxB genes, as mutually exclusive models explaining their emergence are still contested. I have identified and annotated the SoxB of several invertebrate taxa. In total, my investigation includes 24 different metazoan taxa, and represents the largest investigation of arthropod SoxB phylogeny to date. In light of this research, I have proposed a new model of SoxB evolution which resolves the conflicting elements of the two primary competing models. Second, to study the evolution of SoxB in terms of functional conservation/divergence, I selected the emerging model organism Tribolium castaneum to draw a comparative analysis with Drosophila melanogaster. I first began by characterising the spatiotemporal expression patterns of SoxNeuro mRNA in early Tribolium embryos using whole mount in situ hybridisation, and examined published Dichaete expression patterns in the context of central nervous system development in T. castaneum. Using these data, I draw a comparison to the expression profiles of Dichaete and SoxNeuro orthologues in Drosophila melanogaster and other species. I have found that both Dichaete and SoxNeuro expression patterns in the developing central nervous system are remarkably well-conserved across species. I also attempted to characterise genome-wide binding for both Dichaete and SoxNeuro proteins in Tribolium in what would have represented the first genomic investigation of its kind in this emerging species. Using a tethered DNA adenine methyltransferase (Dam) enzyme for both SoxNeuro and Dichaete, I hoped to characterise the genomic loci with which each protein interacts within the beetle genome (a technique known as DamID). Unfortunately, these last set of experiments have proved unsuccessful, despite several attempts which have made use of different promoters, different DNA enrichment methodologies, and tackling unforeseen DNA contamination issues. Nevertheless, the troubleshooting experiments that I have carried out will pave the way for further genomic experiments in Tribolium, easing the establishment of genomic research in this emerging organism.