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INTRODUCTION: Motivational experiments allow for assessing the inner drive of the subject to carry out a particular task. For this purpose the Skinner box is widely used. It allows the animal to acquire a conditional response, which can be used to measure the level of motivation. Adipose tissue is involved in maintaining body energy status. It secrets hormone leptin, which signals the brain about current fat storage. Thus, low level of plasma leptin elicits hunger and other responses of the organism related e.g. fertility. AIM(S): In the study we sought to establish a link between plasma leptin level and the level of motivation demonstrated by the animal. METHOD(S): Mice were trained in Skinner box to successfully acquire a conditional response. In addition all animals were calorie restricted (CR) prior to training, to improve performance. Afterwards mice were divided into 3 groups: group fasted for 6 h, group fasted for 24 h and group with CR. Last group of 6 was used as a control, where animals were fed ad libitum. Test was performed on all mice, in which overall lever press was counted during 20 minutes in the Skinner box. Second panel of animals was used to measure the actual plasma leptin level. Animals were sacrificed, blood plasma collected and leptin measurement was carried out using ELISA method. RESULTS: The highest level of motivation was observed in CR only group. Similar result was observed in a group that was fasted for 24 h. Surprisingly the group fasted for 6h only did not show significant differences from control animals. Motivation and plasma leptin level are negatively correlated in our study, with CR animals showing the lowest concentration of hormone. CONCLUSIONS: We demonstrated that calorie restriction is the most crucial factor in controlling motivation level of the animal, compared to short lasting starvation periods. This might be explained by strongly decreasing level of leptin hormone in the animal, when CR is introduced.
INTRODUCTION: PI3K-Akt-mTOR pathway plays important role in long-term synaptic plasticity and memory formation. In our studies describing the Dicer1 gene knock-out model we have shown that improved learning and memory phenotype in these mice was related to up-regulation of the PI3K-Akt-mTOR pathway. In order to prove that the PI3K-Akt-mTOR pathway is crucial for observed phenotype we have generated Pten gene knock-out model in which this up-regulation is achieved by elevation of intracellular levels of phosphatidylinositide 3 in neurons. To examine cognitive functions in Pten model, we have used the IntelliCage system. AIM(S): The puropse of our research was to define the cognitive functions in Pten/CaMKCreERT2 mouse model. METHOD(S): Mouse model: We used Pten/CaMKCreERT2 mouse model in which up-regulation of mTOR activity was generated by mutation of Pten gene restricted to forebrain neurons induced by tamoxifen. Behavioral tests: Following induction of the mutation, Pten mutant mice and controls were tested in learning and memory test in the IntelliCage: a fully automated system for the behavioral assessment of mice that live in social groups. We measured spatial learning with appetitive reinforcement in place preference learning task. RESULTS: Life span: Long-term of PI3K-Akt-mTOR pathway activity in the brain led to increased mutant mice mortality. Pten mutants were able to survive no longer than 13 weeks after the induction of mutation. Place learning in IntelliCage: In the IntelliCage, housing and testing occur in the same cage that is a familiar environment, thus creating a unique opportunity to test behavior for a long-term period in relatively low-stress conditions without handling or social isolation. Using the system, we were able to discover the better performance of Pten mutants in place learning task. Moreover, improved memory was detectable even 24 hours before the death. CONCLUSIONS: Pten/CaMKCreERT2 mice show enhanced memory of rewarded place compare to control littermates. In mutants show decreased life span.
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