Seven rats were trained on Fixed Ratio 20 and two on Fixed Ratio 12 Escape Schedules until a stable baseline was established. Five of the subjects were administered gold thioglucose, three received gold thiomalate, and one was injected with gold, gold thioglucose, and gold thiomalate, allowing for an intrasubject comparison. Colloidal gold appeared to suppress response rate for one or two sessions, while gold thioglucose and gold thiomalate suppressed normal response rates from several to a number of sessions. This response rate suppression was often followed by gradual recovery, although in several subjects recovery of response rate could not be achieved prior to termination of the experiments. The drop in response rate was more consistent for the gold thiomalate-treated subjects than for the gold thioglucose group. A toxic effect of the injected compounds was manifest as a loss of weight, which was regularly associated with a drop in response rate. This weight reduction was greatest in the gold thiomalate-injected animals, indicating that gold thiomalate is probably more toxic than gold thioglucose to rats. Tolerance was developed for gold thioglucose and gold thiomalate, as indicated by smaller response rate decrements after repeated injections of the compound. As a consequence of repeated drug administrations, the animals demonstrated that they could tolerate a 1 milligram per gram of body weight dose of gold thioglucose if the dosage was increased gradually from a low-dosage initial injection. This dosage of 1 milligram per gram of body weight is double the amount required to produce demonstrable hypothalamic lesions in the rat. Previous investigations have failed to demonstrate this degree of tolerance in rats, primarily because the animals did not have the opportunity to adapt themselves to this treatment. Decrease in spontaneous activity on a balance beam apparatus was observed in several rats following administration of the larger gold thioglucose dosages (i.e., 0.5 milligrams per gram of body weight to 1.0 milligram per gram of body weight), as well as following the administration of gold thiomalate. Dosages of 20 milligrams to 50 milligrams of gold chloride were lethal to two rats. The heavy dosage of gold thioglucose administered to the female rat subjects at Utah State University (i.e., up to 1 mg per gram of body weight), although potentially producing extensive hypothalamic lesions, did not produce demonstrable hyperphagia or obesity, probably due to the anorexia and hypophagia associated with liver and kidney damage,which could counteract the hyperphagia expected to be associated with the extensive hypothalamic lesions produced at dosages over 0.5 milligram per gram of body weight following gold thioglucose administration.

<p>This thesis is focused on the heparan sulphate (HS) structure from blind mole rat liver. HS is a glycosaminoglycan that is produced as a proteoglycan, in which linear polysaccharide chains are attached covalently to a protein core. Proteoglycans are widespread molecules in the body and have many important physiological functions. HS is synthesized as a polymer of alternating glucuronic acid and N-acetylglucosamine units. Parts of the polymer are subsequently modified by N-deacetylation /N-sulphation of the glucosamine units, C-5 epimerization of glucuronic acid to iduronic acid and O-sulphation at various positions.</p><p>The mole rats are from Israel and are of the Spalax ehrenbergi superspecies. Spalax Judaei (S60) has 60 chromosomes and Spalax Galili (S52) has 52 chromosomes. They are both completely blind and spend their entire life underground in hypoxic conditions. Spalax Galili (S52) inhabits the cool-humid Upper Galilee Mountains and Spalax Judaei (S60) inhabits the warm-dry southern regions. There is no current information about the heparan sulphate structure of these animals.</p><p>The two blind mole rats (S52 and S60) were metabolically labelled with [3H] Glucosamine. The animals were sacrificed and the organs were taken and frozen. The liver was chosen for the purpose of my project.</p><p>The HS structure was studied using various chromatographic methods such as ion-exchange and gel filtration. Structural analysis of HS indicated that the size of HS from the liver was the same in both species. However, the domain structure differed between the two animals, particularly with regard to sample S52(1) which had obvious differences. This leads to the study of the heparanase cleavage sites. Disaccharide composition analysis identified varying proportions of disaccharide species in S52 and also the possibility of an unknown disaccharide species.</p>

RESUME Le rat Dumbo présente un aspect malformatif évoquant certains syndromes crânio-faciaux humains. La compréhension du phénotype Dumbo pourrait expliquer les événements cellulaires et moléculaires à l’origine de ces syndromes. Le données recueillies chez le rat Dumbo et comparées à celles du rat Wistar sont susceptibles de constituer de précieuses informations éventuellement transposables à l’espèce humaine. La première étape de cette étude a consisté en des analyses morphologiques et morphométriques afin de vérifier les perturbations morphologiques communes entre les rats Dumbo et les syndromes malformatifs humains : la brièveté des os zygomatique, maxillaire, mandibulaire et la position basse des oreilles. Ces analyses ont été réalisées sur les squelettes embryonnaires âgés de 16 jours à 21 jours de rats Dumbo et Wistar à l’aide d’une coloration in toto au Bleu Alcian – Alizarine. La deuxième étape de cette étude consistait en une analyse cytogénétique. Pour ce faire, nous avons établi le caryotype du rat Dumbo et nous l’avons comparé avec le caryotype du rat Wistar. L’étape suivante fut de procéder à l’analyse histologique des malformations crânio-faciales chez le rat Dumbo en observant la chondrogenèse pendant la morphogenèse crânio-faciale. Enfin, l’examen de l’expression des gènes Msx1 sens (S) , Msx1 antisens (AS) et Dlx1 dans l’extrémité céphalique des rats Dumbo a été réalisé par les techniques de RT–PCR (Reverse Transcription Polymerase Chain Reaction method). Des estimations semi-quantitatives ont été validées en utilisant des dilutions ADNc du rat Wistar. Des densitométries de la densité d’amplicons fluorescence ont été réalisées à l’aide du logiciel VilberLourmat Bio1D software. Les résultats obtenus ont permis de caractériser de manière précise les malformations crânio-faciales chez le rat Dumbo. 1- l’analyse céphalométrique sur les squelettes embryonnaires met en évidence une réduction des dimensions de certaines structures crânio-faciales chez le rat Dumbo : os mandibulaire, maxillaire, zygomatique, ainsi qu’on l’observe également dans le syndrome de Treacher Collins. 2- l’analyse cytogénétique par les techniques de banding G ne montre pas une différence entre le caryotype de Dumbo et le caryotype de rat Wistar (le contrôle). 3- l’analyse histologique de têtes d’embryons montre un retard dans les processus de la chondrification et de l’ossification pendant la morphogenèse crânio-faciale avec une croissance retardée des ébauches oculaires et des bourgeons dentaires. 4- l’analyse de l’expression génique de certains gènes homéobox (Msx1 S et AS) et Dlx1 montre une réduction de ces expressions pendant la morphogenèse crânio-faciale chez le rat Dumbo en comparaison avec la morphogenèse normale dans la souche Wistar.

No description available.

No description available.

This thesis is focused on the heparan sulphate (HS) structure from blind mole rat liver. HS is a glycosaminoglycan that is produced as a proteoglycan, in which linear polysaccharide chains are attached covalently to a protein core. Proteoglycans are widespread molecules in the body and have many important physiological functions. HS is synthesized as a polymer of alternating glucuronic acid and N-acetylglucosamine units. Parts of the polymer are subsequently modified by N-deacetylation /N-sulphation of the glucosamine units, C-5 epimerization of glucuronic acid to iduronic acid and O-sulphation at various positions. The mole rats are from Israel and are of the Spalax ehrenbergi superspecies. Spalax Judaei (S60) has 60 chromosomes and Spalax Galili (S52) has 52 chromosomes. They are both completely blind and spend their entire life underground in hypoxic conditions. Spalax Galili (S52) inhabits the cool-humid Upper Galilee Mountains and Spalax Judaei (S60) inhabits the warm-dry southern regions. There is no current information about the heparan sulphate structure of these animals. The two blind mole rats (S52 and S60) were metabolically labelled with [3H] Glucosamine. The animals were sacrificed and the organs were taken and frozen. The liver was chosen for the purpose of my project. The HS structure was studied using various chromatographic methods such as ion-exchange and gel filtration. Structural analysis of HS indicated that the size of HS from the liver was the same in both species. However, the domain structure differed between the two animals, particularly with regard to sample S52(1) which had obvious differences. This leads to the study of the heparanase cleavage sites. Disaccharide composition analysis identified varying proportions of disaccharide species in S52 and also the possibility of an unknown disaccharide species.

Drug abuse peaks during adolescence, and exposure to drugs during adolescence predicts drug abuse in adulthood. Nevertheless, adolescence is not widely studied in animal models of drug intake. Moreover, few studies have investigated sex differences in drug-reinforced behavior during adolescence. We studied age- and sex-differences in acquisition and maintenance of amphetamine self-administration in Sprague-Dawley rats. Adolescent males took more amphetamine than adult males, supporting the hypothesis that adolescents are more sensitive to amphetamine. A high rate of “inappropriate” active lever presses among periadolescent males suggests impulsive behavior. In the maintenance phase of testing, young adult males failed to work as hard as adult males. In contrast, young adult females worked harder than adult females. Comparing sex groups, young adult females worked harder than age-matched males to obtain amphetamine. These results will ultimately help to form effective treatment and prevention programs for drug dependent individuals of all ages and both sexes.

The goal of my thesis was to elucidate the impact of protein-energy malnutrition (PEM, a condition commonly found in aging stroke patients) on outcomes from global ischemia. I first examined the hypothesis that PEM will impair working memory in the adult gerbil as measured in the T-maze. Gerbils were fed an adequate (12.5%) or low protein (2%; PEM) diet for 6wk. Stringent assessment of T-maze performance indicated an improvement with PEM although I was unable to reconcile whether this was increased motivation for the food reward or enhanced working memory.<p> The second hypothesis tested was PEM will decrease expression of plasticity-associated hippocampal mRNA and protein expression following global ischemia in the gerbil. The plasticity markers brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (trkB), and growth-associated protein-43 (GAP-43) were examined in the CA1 hippocampal region post-ischemia. PEM induced in gerbils for 4wk did not alter the global ischemia-induced decrease in CA1 neurons. Ischemia resulted in increased CA1 pyramidal expression of BDNF and trkB mRNA at 1, 3, and 7d post-ischemia and increased trkB protein expression at 3 and 7d. PEM further elevated the increased trkB protein detected at 7d in the fibres. Ischemia resulted in increased GAP-43 protein at 3 and 7d post-ischemia with PEM increasing this expression at 3d in the CA3 and hilar regions in addition to CA1. These findings suggest an increased stress-response and/or hyperexcitability state in the hippocampus of malnourished ischemic animals.<p> Since the reliability of the gerbil model of global ischemia has come into question, the third part of my thesis tested the hypothesis that the influence of pre-existing PEM on global ischemia-induced hippocampal injury can be reliably studied with the 2-vessel occlusion rat model. The impact of PEM on CA1 neuronal death and dendritic damage was examined. Rats received protein adequate (18%) or deficient (2%; PEM) diet for 7-8d prior to global ischemia. PEM did not worsen the decrease in CA1 neurons and dendrites observed at 7d post-ischemia. Importantly, I found that PEM altered blood glucose and acid-base balance during surgery and caused brief hypothermia post-surgically, factors which are important for consistent brain injury.<p> Taken together, these findings reveal (i) that nutritional care, although frequently ignored, can have robust effects on recovery mechanisms after brain ischemia; and (ii) the challenges of studying pre-existing PEM in an established rodent model of stroke.

The goal of my thesis was to elucidate the impact of protein-energy malnutrition (PEM, a condition commonly found in aging stroke patients) on outcomes from global ischemia. I first examined the hypothesis that PEM will impair working memory in the adult gerbil as measured in the T-maze. Gerbils were fed an adequate (12.5%) or low protein (2%; PEM) diet for 6wk. Stringent assessment of T-maze performance indicated an improvement with PEM although I was unable to reconcile whether this was increased motivation for the food reward or enhanced working memory.<p> The second hypothesis tested was PEM will decrease expression of plasticity-associated hippocampal mRNA and protein expression following global ischemia in the gerbil. The plasticity markers brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (trkB), and growth-associated protein-43 (GAP-43) were examined in the CA1 hippocampal region post-ischemia. PEM induced in gerbils for 4wk did not alter the global ischemia-induced decrease in CA1 neurons. Ischemia resulted in increased CA1 pyramidal expression of BDNF and trkB mRNA at 1, 3, and 7d post-ischemia and increased trkB protein expression at 3 and 7d. PEM further elevated the increased trkB protein detected at 7d in the fibres. Ischemia resulted in increased GAP-43 protein at 3 and 7d post-ischemia with PEM increasing this expression at 3d in the CA3 and hilar regions in addition to CA1. These findings suggest an increased stress-response and/or hyperexcitability state in the hippocampus of malnourished ischemic animals.<p> Since the reliability of the gerbil model of global ischemia has come into question, the third part of my thesis tested the hypothesis that the influence of pre-existing PEM on global ischemia-induced hippocampal injury can be reliably studied with the 2-vessel occlusion rat model. The impact of PEM on CA1 neuronal death and dendritic damage was examined. Rats received protein adequate (18%) or deficient (2%; PEM) diet for 7-8d prior to global ischemia. PEM did not worsen the decrease in CA1 neurons and dendrites observed at 7d post-ischemia. Importantly, I found that PEM altered blood glucose and acid-base balance during surgery and caused brief hypothermia post-surgically, factors which are important for consistent brain injury.<p> Taken together, these findings reveal (i) that nutritional care, although frequently ignored, can have robust effects on recovery mechanisms after brain ischemia; and (ii) the challenges of studying pre-existing PEM in an established rodent model of stroke.

The brain undergoes structural changes in response to new experiences like learning a new skill. Skilled motor movements depend greatly on the primary motor cortex for their execution. Recent studies describe rat strain differences in motor performance related to differential synaptic efficacy in the motor cortex of rats. Previous studies identified differences in motor performance related to differential dendritic morphology and strain related differences in synaptic function in the motor cortex. Strain differences are one way of investigating anatomical organization and behaviour of the motor system. The object of this research was to examine strain related differences in dendritic morphology in layer II / III pyramidal cells of the forelimb area of the sensory motor cortex in both Long-Evans and Fischer 344 rats after reach training. This research also examined whether changes in reaching behaviour could be attributed to changes in dendritic morphology. Rats were trained once a day for 30 days to reach for a food pellet through a slot in a reaching box. Pyramidal cells in the motor sensory forelimb (MSF) cortex were stained with the Golgi Cox method. Subsequent analysis of Sholl and branch order data of cell drawings determined that there were no significant differences in any measure of dendritic length or dendritic length at branch order 3, 4, 5 of pyramidal cells in layer II/III of the MSF cortex between the Long Evans and Fischer 344 rat strain. The only significant strain related difference was that the Fischer 344 strain exhibited fewer reaches for each food pellet obtained, demonstrating greater reaching proficiency than similarly trained Long-Evans rats. These findings suggest that further research examining strain comparisons is required to understand the neural mechanisms underlying the differences in motor behaviour observed in these rat strains. / October 2006