A change in hippocampal protocadherin gamma expression in a learned helpless rat

• Microarray of cLH Rat hippocampus implicate several pathways involved in depression.
• Also shows elevated protocadherin-γA11 expression in cLH rats.
• Pcdhga11 expression results in approximately 40% higher PCDHGA11 levels.
• Difference appears to be primarily due to change in CA1 region.

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 learned helplessness, a model of depression, presents an opportunity to search for genes affecting the depressive symptoms found in the helpless model which may provide clues toward understanding the human disease. A microarray study 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-protocadherins for further study to determine the basis for the change in expression. Helpless animals demonstrated an increased expression primarily in CA1 neurons. Protocadherins have been implicated in synapse development and these results suggest they may play a role related to the reduced neuroplasticity observed in depression. Additionally, a number of genes linked to pathways known or suspected to be involved in depression were also detected, these will require further verification and study.