RT Journal Article SR Electronic T1 Nicotine Acts on Cholinergic Signaling Mechanisms to Directly Modulate Choroid Plexus Function JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0051-19.2019 DO 10.1523/ENEURO.0051-19.2019 VO 6 IS 2 A1 Lallai, Valeria A1 Grimes, Nickolas A1 Fowler, James P. A1 Sequeira, P. Adolfo A1 Cartagena, Preston A1 Limon, Agenor A1 Coutts, Margaret A1 Monuki, Edwin S. A1 Bunney, William A1 Demuro, Angelo A1 Fowler, Christie D. YR 2019 UL http://www.eneuro.org/content/6/2/ENEURO.0051-19.2019.abstract AB Neuronal cholinergic circuits have been implicated in cognitive function and neurological disease, but the role of cholinergic signaling in other cellular populations within the brain has not been as fully defined. Here, we show that cholinergic signaling mechanisms are involved in mediating the function of the choroid plexus, the brain structure responsible for generating CSF and releasing various factors into the brain. The choroid plexus was found to express markers of endogenous cholinergic signaling, including multiple nicotinic acetylcholine receptor (nAChR) subtypes in a region-specific manner, and application of nicotine was found to induce cellular activation, as evidenced by calcium influx in primary tissue. During intravenous nicotine self-administration in male rats, nicotine increased expression of transthyretin, a protein selectively produced and released by the choroid plexus, and microRNA-204 (mir-204), a transcript found in high levels in the choroid plexus and CSF. Finally, human choroid plexus tissue from both sexes was found to exhibit similar nAChR, transthyretin and mir-204 expression profiles, supporting the translational relevance of the findings. Together, these studies demonstrate functionally active cholinergic signaling mechanisms in the choroid plexus, the resulting effects on transthyretin and mir-204 expression, and reveal the direct mechanism by which nicotine modulates function of this tissue.