Project description:We are searching for common gene expression alteration in the hippocampus of animal models of learning disabilities and in post-mortem human tissues derived from patients with cognitive deficits. Our study has three phases. In phase I, we want to investigate the changes in gene expression in a transgenic mouse line that shows impairments in hippocampal-dependent learning. These animals are overexpressing the RNA-binding protein HuD in the forebrain under the control of the alpha CAMKinII promoter. For phase II, we plan to characterize the hippocampus of another animal model of learning disabilities: fetal alcohol exposed (FAE) rats. Last, for phase III, we would like to examine gene expression changes in the hippocampus and other tissues from patients with schizophrenia. To test our hypothesis, in phase 2 of our project, we propose to compare the pattern of gene expression in our mouse model with that in the hippocampus of rats prenatally exposed to alcohol (FAE model). Our hypothesis is that learning disabilities have common neural substrates regardless of the origin of the disability being genetic, environmental of a combination of these two. To test this hypothesis, we plan to examine the pattern of gene expression in the hippocampus of animals and humans with cognitive deficits and use bioinformatics tools to identify common changes in gene expression in three of such conditions: a genetic model (HuD transgenic mice), an environmental model (FAE rats) and a model for combined environmental and genetic effects (patients with schizophrenia). All the animals are adult male Sprague-Dawley rats (age 90-100 days). Animals were divided in three diet groups and three experimental treatment conditions (9 conditions altogether). Three groups of pregnant rat dams were placed on different diet regimens: a liquid diet containing 5% alcohol (A) groups, a control group fed an isocaloric liquid diet without alcohol (B) and a group of rats fed lab chow ad libitum (C). Offspring from each of these groups were allowed to grow until adulthood and placed into each of three training groups: a contextual fear conditioned group (1), a non-learning stress control group (2) and a naive/unhandled group (3). Hippocampi were dissected and used to isolate total RNA from each rat diet and training condition. Initially, we will submit 18 samples as follows: 10 samples from training group 1 and 8 samples from training group 3 (training group 2 will be analyzed at a later date). The diet assignment for the 18 samples is: 8 samples from group A, 6 samples of group B and 4 samples of group C. Please note that I was able to enter only the first 8 samples, as the sample list does not hold 18 samples altogether.

Project description:We are searching for common gene expression alteration in the hippocampus of animal models of learning disabilities and in post-mortem human tissues derived from patients with cognitive deficits. Our study has three phases. In phase I, we want to investigate the changes in gene expression in a transgenic mouse line that shows impairments in hippocampal-dependent learning. These animals are overexpressing the RNA-binding protein HuD in the forebrain under the control of the alpha CAMKinII promoter. For phase II, we plan to characterize the hippocampus of another animal model of learning disabilities: fetal alcohol exposed (FAE) rats. Last, for phase III, we would like to examine gene expression changes in the hippocampus and other tissues from patients with schizophrenia. To test our hypothesis, in phase 2 of our project, we propose to compare the pattern of gene expression in our mouse model with that in the hippocampus of rats prenatally exposed to alcohol (FAE model). Our hypothesis is that learning disabilities have common neural substrates regardless of the origin of the disability being genetic, environmental of a combination of these two. To test this hypothesis, we plan to examine the pattern of gene expression in the hippocampus of animals and humans with cognitive deficits and use bioinformatics tools to identify common changes in gene expression in three of such conditions: a genetic model (HuD transgenic mice), an environmental model (FAE rats) and a model for combined environmental and genetic effects (patients with schizophrenia). All the animals are adult male Sprague-Dawley rats (age 90-100 days). Animals were divided in three diet groups and three experimental treatment conditions (9 conditions altogether). Three groups of pregnant rat dams were placed on different diet regimens: a liquid diet containing 5% alcohol (A) groups, a control group fed an isocaloric liquid diet without alcohol (B) and a group of rats fed lab chow ad libitum (C). Offspring from each of these groups were allowed to grow until adulthood and placed into each of three training groups: a contextual fear conditioned group (1), a non-learning stress control group (2) and a naive/unhandled group (3). Hippocampi were dissected and used to isolate total RNA from each rat diet and training condition. Initially, we will submit 18 samples as follows: 10 samples from training group 1 and 8 samples from training group 3 (training group 2 will be analyzed at a later date). The diet assignment for the 18 samples is: 8 samples from group A, 6 samples of group B and 4 samples of group C. Please note that I was able to enter only the first 8 samples, as the sample list does not hold 18 samples altogether. Keywords: dose response

Project description:Thiazolidinediones (TZDs) are agonists at peroxisome proliferator-activated gamma-type (PPAR-y) receptors and are used clinically for the treatment of type 2 diabetes where they have been shown to reestablish insulin sensitivity, improve lipids profile, and reduce inflammation. Recent work also suggests that TZDs may be beneficial in Alzheimer's disease (AD), ameliorating cognitive decline early in the disease process. However, there have been only a few studies identifying mechanisms through which cognitive benefits may be exerted. Starting at 10 months of age, the triple transgenic mouse model of AD (3xTg-AD) with accelerated amyloid-B (AB) deposition and tau pathology was treated with the TZD pioglitazone (PIO- Actos) at 18 mg/Kg body weight/day. After four months, PIO-treated animals showed multiple beneficial effects, including improved learning on the active avoidance task, reduced serum cholesterol, decreased hippocampal AB deposits, and enhanced short- and long-term plasticity. Baseline electrophysiological membrane properties and blood glucose levels were unchanged by PIO treatment. Gene microarray analyses of hippocampal tissue identified predicted transcriptional responses following TZD treatment as well as potentially novel targets of TZDs, including facilitation of estrogenic processes, and decreases in glutamatergic and ketone metabolic/ cholesterol dependent processes. Taken together, these results confirm prior animal studies showing that TZDs can ameliorate cognitive deficits associated with AD-related pathology, but also extend these findings by pointing to novel molecular targets in the brain. Keywords : Hippocampus; LTP; Microarray analysis; Avoidance learning; Aging; PPAR; Synaptic hyperpolarization; T2DM We used the 3xTg-AD mouse model of Alzheimer's disease and monitored the effects of pioglitazone (PIO-Actos a TZD) on behavioral, electrophysiological, and molecular variables. Emphasis was placed on identifying hippocampal PIO-sensitive genes that were also associated with learning and memory processes. Starting at 10 months of age, female mice were treated for approximately 14 weeks with either a control diet or a PIO-containing diet. PIO was incorporated into the diet to yield a final dose of approximately 18 mg/kg body weight/day.

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Syracuse High/Low Avoidance Learning in Rats

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