Cytidine-5-diphosphate (CDP)-Choline

Effects of CDP-choline treatment on neurobehavioral deficits after TBI and on hippocampal and neocortical acetylcholine release.
Dixon CE, Ma X, Marion DW.
J Neurotrauma. 1997 Mar;14(3):161-9.

 The exogenous administration of cytidine-5′-diphosphate (CDP)-choline has been used extensively as a brain activator in different neurological disorders that are associated with memory deficits. A total of 50 rats were utilized to (a) determine whether exogenously administered CDP-choline could attenuate posttraumatic motor and spatial memory performance deficits and (b) determine whether intraperitoneal (i.p.) administration of CDP-choline increases acetylcholine (ACh) release in the dorsal hippocampus and neocortex. In the behavioral study, traumatic brain injury (TBI) was produced by lateral controlled cortical impact (2-mm deformation/6 m/sec) and administered CDP-choline (100 mg/kg) or saline daily for 18 days beginning 1 day postinjury. At 1 day postinjury, rats treated with CDP-choline 15 min prior to assessment performed significantly better than saline-treated rats. Between 14-18 days postinjury, CDP-choline-treated rats had significantly less cognitive (Morris water maze performance) deficits that injured saline-treated rats. CDP-choline treatment also attenuated the TBI-induced increased sensitivity to the memory-disrupting effects of scopolamine, a muscarinic antagonist. The microdialysis studies demonstrated for the first time that a single i.p. administration of CDP-choline can significantly increase extracellular levels of ACh in dorsal hippocampus and neocortex in normal, awake, freely moving rats. This article provides additional evidence that spatial memory performance deficits are, at least partially, associated with deficits in central cholinergic neurotransmission and that treatments that enhance ACh release in the chronic phase after TBI may attenuate cholinergic-dependent neurobehavioral deficits. PMID: 9104933

  Effects of CDP-choline on cognition and cerebral hemodynamics in patients with Alzheimer’s disease.
Caamaño J, Gómez MJ, Franco A, Cacabelos R.
Methods Find Exp Clin Pharmacol. 1994 Apr;16(3):211-8.

 CDP-choline (cytidine-5-diphosphate-choline) is an acetylcholine precursor frequently used in cerebrovascular disorders and psychoorganic syndromes. Furthermore, several authors have demonstrated the positive effects of CDP-choline on cognitive disorders and memory deficits. In the present study, the effects of CDP-choline (1000 mg/day, p.o. for 1 month) on cognition, evaluated by the Mini-Mental State Examination (MMSE) of Folstein et al., and on blood flow velocities, measured by transcranial Doppler ultrasonography (TCD), were investigated in patients with Alzheimer’s disease: (AD, n = 20, age: 66.75 +/- 6.73 years, range: 57-78 yr). Cognitive function was measured by means of the MMSE in basal conditions (A) and after 1 month of treatment with CDP-choline (C). TCD measures were taken through the temporal window for right (MCA-R) and left (MCA-L) middle cerebral arteries with a 2 MHz pulsed transducer using a TC-2000S in basal conditions (A), 1 h after the administration of CDP-choline (B) and after 1 month of treatment with CDP-choline (C). MMSE scores were significantly increased (p < 0.005) in patients with early-onset Alzheimer’s disease (EOAD) after CDP-choline treatment. Moreover, the orientation subtest significantly increased in the global group of AD patients (p < 0.01) and in EOAD patients (p < 0.02). Significant differences (p < 0.05) were also found in MCA-Land MCA-R measures between recordings. These results suggest that CDP-choline influences cognitive and cerebrovascular function in Alzheimer’s disease, probably through a mechanism linked to an immunogenic and/or neurotrophic effect at the microvascular niche. PMID: 7913981

 Oral cytidine 5′-diphosphate choline administration to rats increases brain phospholipid levels.
Agut J, Lopez G-Coviella I, Ortiz JA, Wurtman RJ.
Ann N Y Acad Sci. 1993 Sep 24;695:318-20.

 Exogenous cytidine 5′diphosphocholine (CDP-choline) is completely metabolized to circulating cytidine and choline. Both compounds enter the brain and can be used in phosphatidylcholine (PC) synthesis via the Kennedy (CDP-choline) cycle. We administered oral CDP-choline to 12 month-old rats (500 mg/kg/day) for 21, 42, or 90 days to determine whether this treatment would alter brain levels of PC and the other structural phospholipids, phosphatidylserine (PS) and phosphatidylethanolamine (PE). After 42 days, brain PC levels increased significantly (p < 0.01) by 23.3%; after 90 days PC increased by 30% (p < 0.01), PS by 37.2% (p < 0.01), and PE by 13% (not significant). The ratios of each of the phospholipids to total membrane phospholipids were unchanged. These data demonstrate that repeated oral CDP-choline administration can increase the amounts of phospholipids in brain membranes, thus providing a rationale for using this compound in brain diseases that damage neurons. PMID: 8239304

  The effect of cytidine-diphosphate choline (CDP-choline) on brain lipid changes during aging.
De Medio GE, Trovarelli G, Piccinin GL, Porcellati G.
J Neurosci Res. 1984;11(1):49-58.

 Lipid synthesis has been tested in vivo in different brain areas of 12-month-old male rats. Cortex, striatum, brainstem, and subcortex of brain have been examined. The cerebellum was discarded. Mixtures of (2-3H) glycerol and (Me-14C) choline were injected into the lateral ventricle of the brain as lipid precursors, and their incorporation into total lipid, water-soluble intermediates and choline-containing phospholipids was examined 1 hr after isotope injection. In another series of experiments cytidine-5′-diphosphate choline (CDP-choline) was injected intraventricularly to the aged rats 10 min before sacrifice with a simultaneous injection, and radioactivity assays were performed as above. Distribution of radioactivity content of CDP-choline among brain areas 10 min after its administration showed a noticeable enrichment of the nucleotide and water-soluble-related compounds in the examined areas, but to a lesser degree in the cerebral cortex. The incorporation of labelled glycerol, which is severely depressed in aged rats in all four areas [Gaiti et al, 1982, 1983], was increased only in the cortex, and apparently decreased in the other areas. This last result is probably due to a dilution effect brought about by the administered cold CDP-choline upon the (14C)-containing water-soluble metabolites. As a consequence, the (3H)/(14C) ratio in total lipid and in isolated phosphatidylcholine and choline plasmalogen increased after CDP-choline treatment. PMID: 6708133