CDP Choline

BACKGROUND: Globally, stroke is the second leading cause of death and disability. In different studies conducted previously, the choline-containing phospholipids citicoline and choline alphoscerate have been proposed as adjuvants in the treatment of acute strokes. A systematic review was conducted to provide updated information on the effects of citicoline and choline alphoscerate in patients with acute and hemorrhagic strokes. METHODS: PubMed/Medline, Scopus, and Web of Science were searched to identify relevant materials...

BACKGROUND: Cognitive operations including pre-attentive sensory processing are markedly impaired in patients with schizophrenia (SCZ) but evidence significant interindividual heterogeneity, which moderates treatment response with nicotinic acetylcholine receptor (nAChR) agonists. Previous studies in healthy volunteers have shown baseline-dependency effects of the α7 nAChR agonist cytidine 5'-diphosphocholine (CDP-choline) administered alone and in combination with a nicotinic allosteric modulator (galantamine) on auditory deviance detection measured with the mismatch negativity (MMN) event-related potential (ERP)...

The CDP-choline (Kennedy) pathway culminates with the synthesis of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) by choline/ethanolamine phosphotransferase 1 (CEPT1) in the endoplasmic reticulum (ER), and PC synthesis by choline phosphotransferase 1 (CHPT1) in the Golgi apparatus. Whether the PC and PE synthesized by CEPT1 and CHPT1 in the ER and Golgi apparatus has different cellular functions has not been formally addressed. Here we used CRISPR editing to generate CEPT1-and CHPT1-knockout (KO) U2OS cells to assess the differential contribution of the enzymes to feed-back regulation of nuclear CTP:phosphocholine cytidylyltransferase (CCT)α, the rate-limiting enzyme in PC synthesis, and lipid droplet (LD) biogenesis...

BACKGROUND: Citicoline or CDP-choline is a neuroprotective/neurorestorative drug used in several countries for the treatment of traumatic brain injury (TBI). Since the publication of the controversial COBRIT, the use of citicoline has been questioned in this indication, so it was considered necessary to undertake a systematic review and meta-analysis to evaluate whether citicoline is effective in the treatment of patients with TBI. METHODS: A systematic search was performed on OVID-Medline, EMBASE, Google Scholar, the Cochrane Central Register of Controlled Trials, ClinicalTrials...

The term mild cognitive impairment (MCI) defines an intermediate state between normal aging and dementia. Vascular cognitive impairment refers to a decline in cognitive function that is caused by or associated with vascular disease and comprises all the spectrum of cognitive impairments, from MCI of vascular origin to vascular dementia. One of the available treatments for cognitive impairment is cytidine diphosphate-choline (CDP-Choline), or citicoline. The objective of the present manuscript is to provide complete evidence about the efficacy of citicoline for MCI, especially of vascular origin, but also due to other neurodegenerative disorders...

UNLABELLED: Glycerophospholipids including phosphatidylethanolamine (PE) and phosphatidylcholine (PC) are vital components of biological membranes. Trypanosomatid parasites of the genus Leishmania can acquire PE and PC via de novo synthesis and the uptake/remodeling of host lipids. In this study, we investigated the ethanolaminephosphate cytidyltransferase (EPCT) in Leishmania major , which is the causative agent for cutaneous leishmaniasis. EPCT is a key enzyme in the ethanolamine branch of the Kennedy pathway which is responsible for the de novo synthesis of PE...

Antenatal steroid administration to pregnant women at risk of prematurity provides pulmonary maturation in infants, while it has limited effects on incidence of bronchopulmonary dysplasia (BPD), the clinical expression of hyperoxia-induced lung injury (HILI). Cytidine-5'-diphosphate choline (CDP-choline) was shown to alleviate HILI when administered to newborn rats. Therefore, we investigated effects of maternal administration of CDP-choline, alone or in combination with betamethasone, on lung maturation in neonatal rats subjected to HILI immediately after birth...

OBJECTIVES: The purpose of this study is to investigate the effects of cholinergic anti-inflammatory pathway (CAP)-activating drugs, choline and citicoline (Cytidinediphosphate-choline, CDP-choline), on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) parameters and the contribution of NADPH Oxidase4 (NOX4) p22phox. BACKGROUND: Endotoxemia induces a systemic inflammatory response characterized by the production of pro-inflammatory mediators and reactive oxygen species (ROS), which eventually develops acute kidney injury (AKI)...

There is a dearth of studies focused on understanding pharmacokinetics, pharmacodynamics and toxicodynamics of polymyxins following direct administration to the central nervous system (CNS). In this study, for the first time, untargeted metabolomics were employed to ascertain the perturbations of brain metabolism in the rat cerebral cortex following direct brain injection of 0.75 mg/kg polymyxin B (1 and 4 h) through the right lateral ventricle. In the right cortex metabolome, ICV polymyxin B induced a greater perturbation at 1 h compared to negligible effect at 4 h...

Autophagy, a conserved eukaryotic intracellular catabolic pathway, maintains cell homeostasis by lysosomal degradation of cytosolic material engulfed in double membrane vesicles termed autophagosomes, which form upon sealing of single-membrane cisternae called phagophores. While the role of phosphatidylinositol 3-phosphate (PI3P) and phosphatidylethanolamine (PE) in autophagosome biogenesis is well-studied, the roles of other phospholipids in autophagy remain rather obscure. Here we utilized budding yeast to study the contribution of phosphatidylcholine (PC) to autophagy...

The roles of choline and of choline-containing phospholipids (CCPLs) on the maintenance and progress of neurovascular unit (NVU) integrity are analyzed. NVU is composed of neurons, glial and vascular cells ensuring the correct homeostasis of the blood-brain barrier (BBB) and indirectly the function of the central nervous system. The CCPLs phosphatidylcholine (lecithin), cytidine 5'-diphosphocholine (CDP-choline), choline alphoscerate or α-glyceryl-phosphorylcholine (α-GPC) contribute to the modulation of the physiology of the NVU cells...

Background: Recent research on animal models of ischemic stroke supports the idea that pharmacological treatment potentially enhancing intrinsic brain plasticity could modulate acute brain damage, with improved functional recovery. One of these new drugs is citicoline, which could provide neurovascular protection and repair effects. Objectives: The objective of this randomized, single-blind experimental study was to evaluate whether the treatment with Rischiaril® Forte was able to restore intracortical excitability measures, evaluated through transcranial magnetic stimulation (TMS) protocols, in patients with acute ischemic stroke...

A fish-rich diet has a beneficial effect on cardiovascular health. The platelet activating factor (PAF) is involved in the development of atherosclerosis, and in vitro results support the regulating action of bioactive nutrients on PAF metabolism. The purpose of this study is to examine whether the consumption of farmed fish fed with an olive-pomace enriched diet (EF) affects PAF metabolism and the markers of inflammation and oxidative stress compared to the consumption of conventionally fed farmed fish (CF)...

This study aimed to evaluate the effect of feeding ethyl cellulose rumen-protected methionine (RPM) on skeletal muscle mRNA abundance during the periparturient period. Sixty multiparous Holstein cows were used in a block design and assigned to either a control or RPM diet. The RPM was supplied from -28 to 60 days in milk (DIM) at a rate of 0.09% (prepartum) or 0.10% (postpartum) of dry matter (DM), ensuring a Lys:Met in the metabolizable protein of ~2.8:1. Muscle biopsies were collected at -21, 1, and 21 DIM...

Peripheral nerve injury (PNI) can result from trauma, surgical resection, iatrogenic injury, and/or local anesthetic toxicity. Damage to peripheral nerves may result in debilitating weakness, numbness, paresthesia, pain, and/or autonomic instability. As PNI is associated with inflammation and nerve degeneration, means to mitigate this response could result in improved outcomes. Numerous nutrients have been investigated to prevent the negative sequelae of PNI. Alpha-lipoic acid, cytidine diphosphate-choline (CDP Choline), curcumin, melatonin, vitamin B12, and vitamin E have demonstrated notable success in improving recovery following PNI within animal models...

Eukaryotic cell membranes are primarily composed of phospholipids, the most abundant of which is phosphatidylcholine (PC). De novo synthesis of PC by the CDP-choline pathway is under the control of the rate-limiting enzyme CTP:phosphocholine cytidylyltransferase (CCT). The nuclear CCTa isoform is regulated by translocation to the inner nuclear membrane (INM) and nuclear lipid droplets (nLD) in response to lipid activators, such as oleate, or deficiency in PC content. CCTa association with the INM is mediated by a positively-charged membrane-binding M-domain and a phosphorylated P-domain containing 16 serine phospho-sites...

Recent investigations reveal that nuclear lipid droplets (nLDs) stimulate lipid metabolic enzymes in response to excess fatty acid loading of cells. For example, in oleate-treated hepatocytes the rate-limiting enzyme in the CDP-choline pathway, CTP:phosphocholine cytidylyltransferase alpha (CCT alpha), is recruited to the surface of nLDs and stimulates the synthesis of phosphatidylcholine (PC). Hepatocyte nLDs derive from ApoB-free LDs in the lumen of the endoplasmic reticulum that migrate into the nucleoplasm through type I nucleoplasmic reticulum invaginations of the inner nuclear membrane (INM)...

BACKGROUND: New drugs for veterinary patients with acute respiratory distress syndrome (ARDS) are urgently needed. Early or late postinfection treatment of influenza-infected mice with the liponucleotide cytidine diphosphocholine (CDP-choline) resulted in decreased hypoxemia, pulmonary edema, lung dysfunction, and inflammation without altering viral replication. These findings suggested CDP-choline could have benefit as adjunctive treatment for ARDS in veterinary patients (VetARDS). OBJECTIVES: Determine if parenterally administered CDP-choline can attenuate mild VetARDS in dogs with aspiration pneumonia...

Development of ARDS in influenza A virus (IAV)-infected mice is associated with inhibition of alveolar type II (ATII) epithelial cell de novo phosphatidylcholine synthesis and administration of the phosphatidylcholine precursor CDP-choline attenuates IAV-induced ARDS in mice. We hypothesized inhibition of phosphatidylcholine synthesis would also impact the function of ATII cell mitochondria. To test this hypothesis, adult C57BL/6 mice of both sexes were inoculated intranasally with 10,000 p.f.u./mouse influenza A/WSN/33 (H1N1)...

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease that is characterized by unexplained physical fatigue unrelieved by rest. Symptoms also include cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. A syndrome clinically similar to ME/CFS has been reported following well-documented infections with the coronaviruses SARS-CoV and MERS-CoV. At least 10% of COVID-19 survivors develop post acute sequelae of SARS-CoV-2 infection (PASC)...