The brain specific protein, delta-catenin, is critical for the maintenance of cortical neuronal structure and function in viv | Posted on:2010-06-30 | Degree:Ph.D | Type:Dissertation | University:University of California, Los Angeles | Candidate:Matter, Cheryl Mary | Full Text:PDF | GTID:1444390002990250 | Subject:Pharmacology | Abstract/Summary: | | Delta (delta)-catenin is a brain specific member of the adherens junction complex that is heavily expressed in neurons and frequently deleted in the severe mental retardation syndrome, Cri-du-Chat (CDCS). Identified through its interaction with presenilin-1 (PS1), the most commonly mutated protein in familial Alzheimer's disease (FAD); delta-catenin localizes within the post-synaptic and dendritic compartments, and is implicated to play a role in dendritic outgrowth via modulation of the actin cytoskeleton. Mice with a targeted disruption of delta-catenin were shown to have severe impairments in hippocampal dependent learning. The mechanisms underlying these deficits are not clearly defined. In vitro, delta-catenin mediates neuronal morphogenesis implicating alterations in neuronal connectivity in contributing to the cognitive deficits in the delta-catenin (-/-) mice. This work addresses the role of delta-catenin in vivo in the maintenance of cortical neuronal structure and function. We found that loss of delta-catenin in vivo results in a progressive loss of dendritic arbor length and decreased dendritic spine stability resulting in a significant reduction in spine density. Accompanying the progressive structural decline, we observe progressive reductions in cortical responsiveness and functional organization to physiological stimuli. Direct electrode stimulation confirmed the presence of a cortical component in the decline in responsiveness. Our data indicates delta-catenin is critical for the maintenance of cortical neuronal structure and function in vivo and may further our understanding of the pathology associated with the mental retardation syndrome Cri-du-Chat and neurodegenerative diseases such as Alzheimer's disease. | Keywords/Search Tags: | Cortical neuronal structure, Delta-catenin, Maintenance | | Related items |
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