Borna Disease Virus Blocks Potentiation of Presynaptic Activity through Inhibition of Protein Kinase C Signaling

• DOI: 10.1371/journal.ppat.0020019
• Publication Date: 2006-03-10T18:07:28Z
• Authors: Romain Volmer; Céline Monnet; Daniel Gonzalez-D...
• Keywords: Neural facilitation

Infection by Borna disease virus (BDV) enables the study of molecular mechanisms whereby a can persist in central nervous system and lead to altered brain function absence overt cytolysis inflammation. This neurotropic infects wide variety vertebrates causes behavioral diseases. The basis BDV-induced impairment remains largely unknown. Here, we investigated whether BDV infection neurons affected synaptic activity, studying rate vesicle (SV) recycling, good indicator activity. Vesicular cycling was visualized cultured hippocampal synapses, using an assay based on uptake antibody directed against luminal domain synaptotagmin I. did not affect elementary presynaptic functioning, such as spontaneous or depolarization-induced vesicular cycling. In contrast, with specifically blocked enhancement SV recycling that is observed response stimuli-induced potentiation, suggesting defects long-term potentiation. Studies signaling pathways involved potentiation revealed this blockade due reduction phosphorylation protein kinase C (PKC) proteins regulate myristoylated alanine-rich substrate (MARCKS) Munc18-1/nSec1. Moreover, interference PKC-dependent identified downstream PKC activation. We also provide evidence phosphoprotein interferes phosphorylation. Altogether, our results reveal new mechanism which cause dysfunction contribute neurobehavioral disorders.