Student Theses and Dissertations

Trudy McCall

Date of Award

2009

Document Type

Thesis

RU Laboratory

McEwen Laboratory

Keywords

hippocampal plasticity, stress, dendritic remodeling, pyramidal cell apical dendrites, EndoN

Abstract

Pyramidal cell apical dendrites in region CA3 of the hippocampus of male rats collapse in size and complexity following chronic stress. These dendrites return to control sizes with a recovery period. This suggests that dendritic remodeling can function as a protective response mechanism, protecting the region from exposure to the increased amounts of excitatory amino acid released in stress. If this is the case, then a situation in which remodeling is prevented during stress should be more damaging to the long-term survival of the organism. To examine this, animals were treated with endo N, an enzyme that cleaves PSA from NCAM for at least 30 days. PSA-NCAM is a cell adhesion molecule present during plasticity in development and also following chronic stress in the hippocampus. PSA-NCAM removal did not cause cell death on its own or following chronic stress by multiple measures. Phosphorylated-Tau is present in the hippocampus of severely damages brains, such as during Alzheimer’s disease. Tau binds to microtubules and helps support the backbone structure making up dendrites and axons. Tau phosphorylates in response to chronic stress, and in animals without PSANCAM, this response was absent. This suggested that the neurons were not as plastic in response to stress. A Golgi stain analysis revealed that PSANCAM removal significantly blunted stress-induced dendritic remodeling. PSA-NCAM removal caused the apical dendrites in CA3 to be larger than control animals both with and without stress. To examine functional consequences of this treatment, animals were put through multiple behavioral tests. PSA-NCAM removal increased the anxiety of rats following chronic stress. Animals also appeared more aggressive when they were housed two per cage. This indicates that without the normal level of dendritic remodeling, chronic stress has increased negative behavioral consequences. Various peptides and receptors were examined, including CART, NPY, and NMDA receptor subunits. PSA removal prevented stress-induced NR2B decreases and NPY increases. Although chronic immobilization stress was not enough to cause long-term damage, a future experiment presenting a insult to the hippocampus following chronic stress in animals with PSANCAM removal could show just how dangerous a lack of dendritic remodeling could be.

Comments

A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy.

Permanent URL

http://hdl.handle.net/10209/427

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