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

• Published in: Journal of chemical neuroanatomy Vol. 96; pp. 1 - 6
• Main Authors: Pati, Sumitra, Ingram, Lishann M., Sun, Min K., Wagner, John J., Cummings, Brian S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2019
• Subjects: Animals; Brain - drug effects; Brain - enzymology; Cerebellum; Choline-Phosphate Cytidylyltransferase - drug effects; Choline-Phosphate Cytidylyltransferase - metabolism; Cocaine; Cocaine - pharmacology; Dopamine Uptake Inhibitors - pharmacology; Hippocampus; Male; Phosphatidylcholine cytidylyltransferase; Rats; Rats, Sprague-Dawley; Cerebellum; CCTβ; CCTα; DAB; IHC; PUFA; MALDI; DAG; ROI; BSA; PC; NLS; CCT; OD; Cocaine; CTP; Hippocampus; Phosphatidylcholine cytidylyltransferase
• ISSN: 0891-0618; 1873-6300
• DOI: 10.1016/j.jchemneu.2018.10.006

•CCTβ, but not CCTα, expression was demonstrated in the rat hippocampus and cerebellum.•CCTβ cellular localization was region-specific, with cytosolic expression detected in Purkinje cells.•Nuclear expression of CCTb was detected in the hippocampus and midbrain.•CCTβ expression was not significantly decreased by cocaine exposure in the hippocampus, corpus callosum or midbrain.•CCTβ expression was significantly decreased by cocaine exposure in the Purkinje cell layer of the cerebellum. 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.