Study of the regulation of BDNF protein synthesis and BDNF protein levels for clinical applications.

Leone, Emiliano
2008-04-15
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Canossa, Marco
Abstract
Brain Derived Neurotrophic Factor (BDNF), a member of the family of neurotrophins, is a key molecule involved in growth, development and modulation of neuronal system. Due to its critical role in a large number of neuronal processes including synaptic plasticity, BDNF altered function and levels are associated even more strongly with many different neuropsychiatric disorders such as schizophrenia and the associated cognitive impairment. In this PhD thesis, we demonstrated that BDNF, which mRNA is transported into dendrites in response to neuronal stimulation, is capable to be translated directly in the dendritic compartment after electrical stimulation. Considering that local protein synthesis (LPS) in dendrites is commonly accepted as a mechanism strongly involved in synaptic plasticity and cognitive processes, we designed a cellular assay based on the detection of BDNF LPS, capable to identify developing compounds able to improve cognitive performances in patients affected by neuropsychiatric disorders. In addition, we studied BDNF protein levels in serum of schizophrenic subjects, finding an alteration of the ratio between BDNF and its precursor form (proBDNF), known to elicits biological effects opposite to mature BDNF on neuronal system. Based on this evidence, we developed an ELISA kit for the measurement of proBDNF/BDNF ratio that could represent a powerful tool for diagnosis of psychosis and for the follow-up of the medical treatment.