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Treatment with Melatonin Improves Cognitive Behavior and Motor Skills in a Rat Model of Liver Fibrosis.

Paola Haeger, Antoine Bouchet, Carolina Ossandon, Gustavo Bresky

Abstract

Introduction and aim. Patients with liver cirrhosis (LC) and minimal hepatic encephalopaty have a higher accident rate. LC impairs the normal sleep-awake cycle and produces disturbances in behavior, cognition and motor skills. Abnormal melatonin (MT) levels have also been identified in LC. Administration of MT may regulate circadian rhythms and prevent the oxidative damage. We studied the effects of MT on spatial memory acquisition (SMA) and motor skills in a liver fibrosis model (LF)s. Materials and methods. Forty-five rats, divided into 4 groups. [G1: LF; G2: LF + MT; G3: MT; G4: Healthy control (HC)]. LF was induced by carbon tetrachloride intraperitoneal injection (0.2 mL/kg) for 5 months. MT was administered during 5 weeks (0.4 mg/kg/day). SMA was evaluated by using the Morris Water Maze protocol where the escape latency (EL) and mean speed were measured. Data were registered by SMART®. Results. The EL measurement analyzed by two way ANOVA: cirrhosis presented a higher EL than controls or those treated with MT suggesting impaired memory acquisition which is rescued by MT treatment. The mean speed analysis revealed that LF presented higher speed than LF+MT or HC, suggesting that LF affects motor skills, which are improved by MT. To discard whether EL is affected by altered motor skills in LF treated with MT, we compared the average EL and speed between days 2 and 6 of the training protocol. Speed was not improved during the trials unlike EL, suggesting that memory acquisition is independent of motor skills. Conclusion. These findings suggest that MT improves cognition and motor skills in the LF model.

Key words. Liver cirrhosis, Hepatic encephalopathy, Melatonin, Motor Skills, Cognitive Behavior

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The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for the Study of the Liver and the Canadian Association for the Study of the Liver

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