Jacob Bell
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Cannabidiol ameliorates cognitive and motor impairments in mice with bile duct ligation
Author(s) Magen I, Avraham Y, Ackerman Z, Vorobiev L, Mechoulam R, Berry EM
Institution Department of Human Nutrition and Metabolism, Braun's School of Public Health, Hadassah-Hebrew University Medical Faculty, 91120 Jerusalem, Israel.
Source J Hepatol 2009 Sep; 51(3):528-34.
MeSH Animals
Bile Ducts
Brain-Derived Neurotrophic Factor
Cannabidiol
Chronic Disease
Cognition
Cognition Disorders
Cyclooxygenase 2
Disease Models, Animal
Female
Gait Disorders, Neurologic
Hepatic Encephalopathy
Ligation
Liver Diseases
Mice
Mice, Inbred Strains
Motor Activity
RNA, Messenger
Receptor, Adenosine A2A
Receptors, Tumor Necrosis Factor, Type I
Treatment Outcome
Triazines
Triazoles
Abstract BACKGROUND/AIMS: The endocannabinoid system in mice plays a role in models of human cirrhosis and hepatic encephalopathy (HE), induced by a hepatotoxin. We report now the therapeutic effects of cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa, on HE caused by bile duct ligation (BDL), a model of chronic liver disease.
METHODS: CBD (5mg/kg; i.p.) was administered over 4weeks to mice that had undergone BDL.
RESULTS: Cognitive function in the eight arm maze and the T-maze tests, as well as locomotor function in the open field test were impaired by the ligation and were improved by CBD. BDL raised hippocampal expression of the TNF-alpha-receptor 1 gene, which was reduced by CBD. However, BDL reduced expression of the brain-derived neurotrophic factor (BDNF) gene, which was increased by CBD. The effects of CBD on cognition, locomotion and on TNF-alpha receptor 1 expression were blocked by ZM241385, an A(2)A adenosine receptor antagonist. BDL lowers the expression of this receptor.
CONCLUSIONS: The effects of BDL apparently result in part from down-regulation of A(2)A adenosine receptor. CBD reverses these effects through activation of this receptor, leading to compensation of the ligation effect.
Language eng
Pub Type(s) Journal Article
Research Support, Non-U.S. Gov't
PubMed ID 19596476
Source: Cannabidiol ameliorates cognitive and motor impairments in mice with bile duct ligation
Author(s) Magen I, Avraham Y, Ackerman Z, Vorobiev L, Mechoulam R, Berry EM
Institution Department of Human Nutrition and Metabolism, Braun's School of Public Health, Hadassah-Hebrew University Medical Faculty, 91120 Jerusalem, Israel.
Source J Hepatol 2009 Sep; 51(3):528-34.
MeSH Animals
Bile Ducts
Brain-Derived Neurotrophic Factor
Cannabidiol
Chronic Disease
Cognition
Cognition Disorders
Cyclooxygenase 2
Disease Models, Animal
Female
Gait Disorders, Neurologic
Hepatic Encephalopathy
Ligation
Liver Diseases
Mice
Mice, Inbred Strains
Motor Activity
RNA, Messenger
Receptor, Adenosine A2A
Receptors, Tumor Necrosis Factor, Type I
Treatment Outcome
Triazines
Triazoles
Abstract BACKGROUND/AIMS: The endocannabinoid system in mice plays a role in models of human cirrhosis and hepatic encephalopathy (HE), induced by a hepatotoxin. We report now the therapeutic effects of cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa, on HE caused by bile duct ligation (BDL), a model of chronic liver disease.
METHODS: CBD (5mg/kg; i.p.) was administered over 4weeks to mice that had undergone BDL.
RESULTS: Cognitive function in the eight arm maze and the T-maze tests, as well as locomotor function in the open field test were impaired by the ligation and were improved by CBD. BDL raised hippocampal expression of the TNF-alpha-receptor 1 gene, which was reduced by CBD. However, BDL reduced expression of the brain-derived neurotrophic factor (BDNF) gene, which was increased by CBD. The effects of CBD on cognition, locomotion and on TNF-alpha receptor 1 expression were blocked by ZM241385, an A(2)A adenosine receptor antagonist. BDL lowers the expression of this receptor.
CONCLUSIONS: The effects of BDL apparently result in part from down-regulation of A(2)A adenosine receptor. CBD reverses these effects through activation of this receptor, leading to compensation of the ligation effect.
Language eng
Pub Type(s) Journal Article
Research Support, Non-U.S. Gov't
PubMed ID 19596476
Source: Cannabidiol ameliorates cognitive and motor impairments in mice with bile duct ligation
