Co-Authors:
Regev, L., Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel
Ezrielev, E., Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel
Gershon, E., Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel
Gil, S., Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel
Chen, A., Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel
Abstract:
Administration of synthetic or purified peptides directly into the brain ventricles is a method commonly used by neuroscientists for exploring physiological and behavioral functions of gene products. i.v. administration is controlled by the blood-brain barrier, which limits its effectiveness, and current approaches for acute or chronic intracerebroventriculardeliveryhave significant technical drawbacks resulting from both the chemical properties of the delivered substance and the experimental procedures. Here we describe a genetic approach for the delivery of secreted peptides or proteins into the cerebrospinal fluid (CSF). Using a choroid plexus-specific promoter, we established a lentiviral-based system, which offers inducible and reversible delivery ofa geneproduct intothe CSF.The functionalityof this system was demonstrated by using the overexpression of the two established neuropeptides, corticotropin-releasing factor and gonadotropin-releasing hormone, modulating anxiety-like behavior and estrus cycle, respectively. We show that this choroid plexus-specific lentiviral-based system is a reliable, effective, and adaptable research tool for intracerebroventricular delivery.