Nicotine Acts on Cholinergic Signaling Mechanisms to Directly Modulate Choroid Plexus Function

Valeria Lallai, Nickolas Grimes, James P. Fowler, P. Adolfo Sequeira, Preston Cartagena, Agenor Limon-Ruiz, Margaret Coutts, Edwin S. Monuki, William Bunney, Angelo Demuro, Christie D. Fowler

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournaleNeuro
Volume6
Issue number2
DOIs
StatePublished - Mar 1 2019
Externally publishedYes

Keywords

  • choroid plexus
  • drug dependence
  • microRNA
  • nicotine
  • nicotinic acetylcholine receptors
  • transthyretin

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Nicotine Acts on Cholinergic Signaling Mechanisms to Directly Modulate Choroid Plexus Function'. Together they form a unique fingerprint.

  • Cite this

    Lallai, V., Grimes, N., Fowler, J. P., Sequeira, P. A., Cartagena, P., Limon-Ruiz, A., Coutts, M., Monuki, E. S., Bunney, W., Demuro, A., & Fowler, C. D. (2019). Nicotine Acts on Cholinergic Signaling Mechanisms to Directly Modulate Choroid Plexus Function. eNeuro, 6(2). https://doi.org/10.1523/ENEURO.0051-19.2019