Neurobiology of the Choroid Plexus Proteome

Samuel Sathyanesan, Psychiatry, Yale University

The choroid plexus (CP) is an important blood-cerebrospinal fluid barrier that is chiefly recognized for its role in cerebrospinal fluid production. Recent progress has shown that the CP expresses high levels of proteins that could be involved in diverse brain functions, including transport of peripheral trophic factors, amyloid –beta clearance, neurotransmitter metabolism, immune response and obesity. Reduced CP function has been implicated in aging and Alzheimer’s disease, while dysregulation of CSF transthyretin, a thyroid hormone distributor protein whose CNS expression is exclusively in the CP, has been linked with depression. The simple cellular composition of the CP and high levels of serotonin receptor (5HT2C) expression render it an ideal system to elucidate signaling networks. The emerging functions of the CP suggest that it is a critical brain structure, that although understudied, holds much potential in the context of neuropsychiatric disorders and their treatment. We have already conducted a detailed genomics analysis of the CP transcriptome and identified over 350 proteins using mass spectrometry techniques. The goals of this proposal are 1) obtain a complete catalog of CP proteins; 2) develop methods to accurately measure the trophic factors expressed in the CP and 3) characterize the 5HT2C signaling network and phosphoproteome. These studies will be accomplished by a combination of proteomics technologies, multidimensional protein identification (MudPIT), multiple reaction monitoring (MRM/MS) and immobilized metal affinity chromatography (IMAC/MS). It is expected that these studies will provide major insight into the function of the blood-CSF barrier and its contribution to overall brain function and homeostasis.