Altered expression of neuroplasticity related genes is associated with pathophysiology of human depression: expression analysis in postmortem human brain of depressed suicide victims (803.13)

Disruptions in normal plasticity mechanisms have been shown to play a part in the etiology of depression. Likewise, chronic stress, a well‐established risk factor for depression, affects plasticity: reduces dendritic spines, synapses, as well as the length and complexity of dendrites in the hippocampus and prefrontal cortex (PFC). GPM6A, a neuronally expressed member of the proteolipid protein family, is a key modulator for neurite and filopodium outgrowth, and synapse formation. Previously, we identified GPM6A gene as a stress‐responsive gene downregulated in the hippocampus in animal models of chronic stress. This effect is reversed by antidepressants. Signaling pathways that mediate GPM6A neuroplastic function and its relevance to human depression are unknown. Here we used qPCR to find out whether GPM6A is relevant to the pathogenesis of human depression. For the first time, we show that GPM6A is transcriptionally downregulated in the postmortem hippocampal tissue of suicide subjects with depression. Using coimmunoprecipitation of GPM6A followed by mass spectrometry we identify calcium/calmodulin dependent protein kinase II α, G protein‐coupled receptor kinase‐interacting protein 1, and coronin 1A to form complexes with GPM6A. We show that also mRNA level of these genes and the coordinated transcriptional response is altered in postmortem brain of depressed suicide subjects. Grant Funding Source : ANPCyT