Localization and expression of CTP: Phosphocholine cytidylyltransferase in rat brain following cocaine exposure

J Chem Neuroanat. 2019 Mar:96:1-6. doi: 10.1016/j.jchemneu.2018.10.006. Epub 2018 Oct 23.

Abstract

Phosphatidylcholine (PC) is a primary phospholipid and major source of secondary lipid messengers and also serves as a biosynthetic precursor for other membrane phospholipids. Phosphocholine cytidylyltransferase (CCT) is the rate-limiting enzyme responsible for catalyzing the formation of PC. Changes in CCT activity have been associated with lipid dysregulation across various neurological disorders. Additionally, intermediates in PC synthesis, such as CDP-choline, have been suggested to attenuate drug craving during cocaine addiction. Recent work from our group demonstrated that cocaine exposure and conditioning alter the level of PC in the brain, specifically in the cerebellum and hippocampus. The present study examines the role of CCT expression in the brain and determines the effect of cocaine exposure on CCT expression. Immunohistochemical analysis (IHC) was performed to assess region-specific expression of CCT, including both of its isoforms; alpha (CCTα) and beta (CCTβ). IHC did not detect any staining of CCTα throughout the rat brain. In contrast, CCTβ expression was detected in the Purkinje cells of the cerebellum with decreases in expression following cocaine exposure. Collectively, these data demonstrate the region- and cell-specific localization of CCTα and CCTβ in the rat brain, as well as the altered expression of CCTβ in the cerebellum following cocaine exposure.

Keywords: Cerebellum; Cocaine; Hippocampus; Phosphatidylcholine cytidylyltransferase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / enzymology
  • Choline-Phosphate Cytidylyltransferase / drug effects*
  • Choline-Phosphate Cytidylyltransferase / metabolism
  • Cocaine / pharmacology*
  • Dopamine Uptake Inhibitors / pharmacology*
  • Male
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Dopamine Uptake Inhibitors
  • Choline-Phosphate Cytidylyltransferase
  • Cocaine