Acetylcholine precursor, citicoline (cytidine 5 ’‐diphosphocholine), reduces hypoglycemia‐induced neuronal death in rats

Abstract Citicoline (cytidine 5’‐diphosphocholine) is an important precursor for the synthesis of neuronal plasma membrane phospholipids, mainly phosphatidylcholine. Administration of citicoline serves as a choline donor for the synthesis of acetylcholine. Citicoline has been shown to reduce the neuronal injury in animal models with cerebral ischemia and in clinical trials of stroke patients. Citicoline is currently being investigated in a multicenter clinical trial. However, citicoline has not yet been examined the context of hypoglycemia‐induced neuronal death. To clarify the therapeutic impact of citicoline in hypoglycemia‐induced neuronal death, we used a rat model with insulin‐induced hypoglycemia. Acute hypoglycemia was induced by intraperitoneal (i.p.) injection of regular insulin (10 U/kg) after overnight fasting, after which iso‐electricity was maintained for 30 minutes. Citicoline injections (500 mg/kg, i.p.) were started immediately after glucose reperfusion. We found that post‐treatment of citicoline resulted in significantly reduced neuronal death, oxidative injury, and microglial activation in the hippocampus when compared to vehicle‐treated control groups at seven days after induced hypoglycemia. Citicoline administration after hypoglycemia decreased immunoglobulin leakage through blood brain barrier disruption in the hippocampus when compared to the vehicle group. Citicoline increased choline acetyltransferase expression for phosphatidylcholine...
Source: Journal of Neuroendocrinology - Category: Endocrinology Authors: Tags: Original Article Source Type: research