Type

Text

Type

Dissertation

Advisor

Canli, Turhan | Henn, Fritz A | Aguirre, Adan | Li, Bo | Peña, Louis.

Date

2014-12-01

Keywords

depression, hippocampus, learned helplessness, major depressive disorder, protocadherin | Genetics

Department

Department of Genetics.

Language

en_US

Source

This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.

Identifier

http://hdl.handle.net/11401/77625

Publisher

The Graduate School, Stony Brook University: Stony Brook, NY.

Format

application/pdf

Abstract

Depression is a disease with a complex etiology that is only beginning to be studied from a genetic perspective. A selectively bred line of rats, susceptible to the learned helplessness model of depression, presents an opportunity to search for genes affecting either the depressive symptoms or the predisposition towards developing the disease. A microarray revealed a small set of genes with altered expression in the hippocampus of the congenitally helpless rats. We selected one of these genes, a member of the γ -protocadherin family, for further study to determine the basis for the change in expression. Helpless animals demonstrated an increased expression of protocadherin gamma A11, primarily in CA1 neurons. In addition, the helpless resistant line displayed changes in expression that favored a more excitotoxic state. Protocadherins have been implicated in synapse development and may alter the connections within the hippocampus in a way that enhances the correlates of depression found in other brain regions of the learned helpless rat. A greater understanding of the function of the clustered protocadherins in the establishment of neuronal networks is required to determine how these molecules affect the functional characteristics of the helpless brain. | 87 pages

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