Human Drug Screening For Memory

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As compounds are optimized by our ROP criteria, we will progress lead compounds towards in vivo efficacy studies, which will be in three well-established and well-accepted mouse models for memory storage. These three tests capture various forms of memory (working memory, object recognition memory and fear memory) in mice and have translational validity for human drug screening for memory disorders. Based on the published data from our lab and others (Ref) our working hypothesis is that positive compounds will enhance memory storage. The following preliminary results support the feasibility of this aim.

C5A.1. Regulation of specific kinesins in mouse hippocampus during contextual fear memory storage: We have studied whether levels of specific kinesins change during memory formation. We selected 6 kinesin genes from the hippocampus (HPC) and carried out qRT-PCR analysis of RNAs from HPC (N=4 biological replications) isolated one hour after contextual fear conditioning (CFC) training, during the initial consolidation of the long-term memory. We identified KIf5B to be significantly upregulated (~1.7 fold, N=4; Students t test, p<0.005) in the HPC following CFC training (Fig ).

C5A.2. Stereotaxic surgeries and delivery of compounds to specific regions of mouse brain. These studies are ongoing in the Puthanveettil lab (Figure XX). An example of such study is shown in Figure XX, where we injected a lentiviral vector to express eGFP in CA1 sub-region of the mouse hippocampus.

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