Journal of Hepatology
Volume 51, Issue 3 , Pages 528-534 , September 2009

Cannabidiol ameliorates cognitive and motor impairments in mice with bile duct ligation

  • Iddo Magen

      Affiliations

    • Department of Human Nutrition and Metabolism, Braun’s School of Public Health, Hadassah-Hebrew University Medical Faculty, 91120 Jerusalem, Israel
    • ,
  • Yosefa Avraham

      Affiliations

    • Department of Human Nutrition and Metabolism, Braun’s School of Public Health, Hadassah-Hebrew University Medical Faculty, 91120 Jerusalem, Israel
    • Corresponding Author InformationCorresponding author. Tel.: +972 2 6757547; fax: +972 2 6431105.
    • ,
  • Zvi Ackerman

      Affiliations

    • Department of Internal Medicine, Hadassah Mount Scopus, Jerusalem, Israel
    • ,
  • Lia Vorobiev

      Affiliations

    • Department of Human Nutrition and Metabolism, Braun’s School of Public Health, Hadassah-Hebrew University Medical Faculty, 91120 Jerusalem, Israel
    • ,
  • Raphael Mechoulam

      Affiliations

    • Department of Medicinal Chemistry and Natural Products, Hadassah-Hebrew University Medical Faculty, Jerusalem, Israel
    • ,
  • Elliot M. Berry

      Affiliations

    • Department of Human Nutrition and Metabolism, Braun’s School of Public Health, Hadassah-Hebrew University Medical Faculty, 91120 Jerusalem, Israel

Received 12 August 2008 ,Revised 18 March 2009 ,Accepted 6 April 2009.

References 

  1. Kountouras J, Billing BH, Scheuer PJ. Prolonged bile duct obstruction: a new experimental model for cirrhosis in the rat. Br J Exp Pathol. 1984;65:305–311
  2. Liu KZ, Man A, Shaw RA, Liang B, Xu Z, Gong Y. Molecular determination of liver fibrosis by synchrotron infrared microspectroscopy. Biochim Biophys Acta. 2006;1758:960–967
  3. Huang LT, Hsieh CS, Chou MH, Chuang JH, Liou CW, Tiao MM, et al. Obstructive jaundice in rats: cause of spatial memory deficits with recovery after biliary decompression. World J Surg. 2004;28:283–287
  4. Montes S, Alcaraz-Zubeldia M, Muriel P, Rios C. Striatal manganese accumulation induces changes in dopamine metabolism in the cirrhotic rat. Brain Res. 2001;891:123–129
  5. Kerfoot SM, D’Mello C, Nguyen H, Ajuebor MN, Kubes P, Le T, et al. TNF-α secreting monocytes are recruited into the brain of cholestatic mice. Hepatology. 2006;43:154–162
  6. Monje ML, Toda H, Palmer TD. Inflammatory blockade restores adult hippocampal neurogenesis. Science. 2003;302:1760–1765
  7. Wu CW, Chen YC, Yu L, Chen HI, Jen CJ, Huang AM, et al. Treadmill exercise counteracts the suppressive effects of peripheral lipopolysaccharide on hippocampal neurogenesis and learning and memory. J Neurochem. 2007;103:2471–2481
  8. Feng R, Rampon C, Tang YP, Shrom D, Jin J, Kyin M, et al. Deficient neurogenesis in forebrain-specific presenilin-1 knockout mice is associated with reduced clearance of hippocampal memory traces. Neuron. 2001;32:911–926
  9. Stella N. Cannabinoid signaling in glial cells. Glia. 2004;48:267–277
  10. Devane WA, Hanuš L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992;258:1946–1949
  11. Mechoulam R, Ben-Shabat S, Hanuš L, Ligumsky M, Kaminski NE, Schatz AR, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol. 1995;50:83–90
  12. Van der Stelt M, Di Marzo V. Anandamide as an intracellular messenger regulating ion channel activity. Prostaglandins Other Lipid Mediat. 2005;77:111–122
  13. Benito C, Tolón RM, Pazos MR, Núñez E, Castillo AI, Romero J. Cannabinoid CB2 receptors in human brain inflammation. Br J Pharmacol. 2008;153:277–285
  14. Avraham Y, Israeli E, Gabbay E, Okun A, Zolotarev O, Silberman I, et al. Endocannabinoids affect neurological and cognitive function in thioacetamide-induced hepatic encephalopathy in mice. Neurobiol Dis. 2006;21:237–245
  15. Dagon Y, Avraham Y, Ilan Y, Mechoulam R, Berry EM. Cannabinoids ameliorate cerebral dysfunction following liver failure via AMP-activated protein kinase. FASEB J. 2007;21:2431–2441
  16. Pacher P, Bátkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2006;58:389–462
  17. Mallat A, Lotersztajn S. Endocannabinoids and liver disease. I. Endocannabinoids and their receptors in the liver. Am J Physiol Gastrointest Liver Physiol. 2008;294:G9–G12
  18. Thomas A, Baillie GL, Phillips AM, Razdan RK, Ross RA, Pertwee RG. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br J Pharmacol. 2007;150:613–623
  19. Mechoulam R, Peters M, Murillo-Rodriguez E, Hanuš LO. Cannabidiol – recent advances. Chem Biodivers. 2007;4:1678–1692
  20. Malfait AM, Gallily R, Sumariwalla PF, Malik AS, Andreakos E, Mechoulam R, et al. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci USA. 2000;97:9561–9566
  21. Ben-Shabat S, Hanuš LO, Katzavian G, Gallily R. New cannabidiol derivatives: synthesis, binding to cannabinoid receptor, and evaluation of their antiinflammatory activity. J Med Chem. 2006;49:1113–1117
  22. Lobato KR, Binfaré RW, Budni J, Rosa AO, Santos AR, Rodrigues AL. Involvement of the adenosine A1 and A2A receptors in the antidepressant-like effect of zinc in the forced swimming test. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32:994–999
  23. Hanuš L, Breuer A, Tchilibon S, Shiloah S, Goldenberg D, Horowitz M, et al. HU-308: a specific agonist for CB(2), a peripheral cannabinoid receptor. Proc Natl Acad Sci USA. 1999;96:14228–14233
  24. Pick CG, Yanai J. Eight arm maze for mice. Int J Neurosci. 1983;21:63–66
  25. Hao S, Avraham Y, Bonne O, Berry EM. Separation-induced body weight loss, impairment in alternation behavior, and autonomic tone: effects of tyrosine. Pharmacol Biochem Behav. 2001;68:273–278
  26. Holm S. A simple sequentially rejective multiple test procedure. Scand J Stat. 1979;6:65–70
  27. Shawcross DL, Davies NA, Williams R, Jalan R. Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. J Hepatol. 2004;40:247–254
  28. Patrignani P, Tacconelli S, Sciulli MG, Capone ML. New insights into COX-2 biology and inhibition. Brain Res Brain Res Rev. 2005;48:352–359
  29. Cauli O, Rodrigo R, Piedrafita B, Boix J, Felipo V. Inflammation and hepatic encephalopathy: ibuprofen restores learning ability in rats with portacaval shunts. Hepatology. 2007;46:514–519
  30. Iosif RE, Ekdahl CT, Ahlenius H, Pronk CJ, Bonde S, Kokaia Z, et al. Tumor necrosis factor receptor 1 is a negative regulator of progenitor proliferation in adult hippocampal neurogenesis. J Neurosci. 2006;26:9703–9712
  31. Gourevitch R, Rocher C, Le Pen G, Krebs MO, Jay TM. Working memory deficits in adult rats after prenatal disruption of neurogenesis. Behav Pharmacol. 2004;15:287–292
  32. Barde YA, Edgar D, Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO J. 1982;1:549–553
  33. Leibrock J, Lottspeich F, Hohn A, Hofer M, Hengerer B, Masiakowski P, et al. Molecular cloning and expression of brain-derived neurotrophic factor. Nature. 1989;341:149–152
  34. Mizuno M, Yamada K, Takei N, Tran MH, He J, Nakajima A, et al. Phosphatidylinositol 3-kinase: a molecule mediating BDNF-dependent spatial memory formation. Mol Psychiatry. 2003;8:217–224
  35. Chan JP, Cordeira J, Calderon GA, Iyer LK, Rios M. Depletion of central BDNF in mice impedes terminal differentiation of new granule neurons in the adult hippocampus. Mol Cell Neurosci. 2008;39:372–383
  36. Carrier EJ, Auchampach JA, Hillard CJ. Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression. Proc Natl Acad Sci USA. 2006;103:7895–7900
  37. Lappas CM, Sullivan GW, Linden J. Adenosine A2A agonists in development for the treatment of inflammation. Expert Opin Investig Drugs. 2005;14:797–806
  38. Fontinha BM, Diógenes MJ, Ribeiro JA, Sebastião AM. Enhancement of long-term potentiation by brain-derived neurotrophic factor requires adenosine A2A receptor activation by endogenous adenosine. Neuropharmacology. 2008;54:924–933
  39. Diógenes MJ, Fernandes CC, Sebastião AM, Ribeiro JA. Activation of adenosine A2A receptor facilitates brain-derived neurotrophic factor modulation of synaptic transmission in hippocampal slices. J Neurosci. 2004;24:2905–2913
  40. Diógenes MJ, Assaife-Lopes N, Pinto-Duarte A, Ribeiro JA, Sebastião AM. Influence of age on BDNF modulation of hippocampal synaptic transmission: interplay with adenosine A2A receptors. Hippocampus. 2007;17:577–585
  41. Tebano MT, Martire A, Potenza RL, Grò C, Pepponi R, Armida M, et al. Adenosine A(2A) receptors are required for normal BDNF levels and BDNF-induced potentiation of synaptic transmission in the mouse hippocampus. J Neurochem. 2008;104:279–286
  42. Shen HY, Coelho JE, Ohtsuka N, Canas PM, Day YJ, Huang QY, et al. Critical role of the adenosine A2A receptor in extrastriatal neurons in modulating psychomotor activity as revealed by opposite phenotypes of striatum and forebrain A2A receptor knock-outs. J Neurosci. 2008;28:2970–2975
  43. Avraham Y, Zolotarev O, Grigoriadis NC, Pautahidis T, Magen I, Vorobiav L, et al. Cannabinoids and capsaicin improve liver function following thioacetamide-induced acute injury in mice. Am J Gastroenterol. 2008;103:3047–3056

☆ The authors who have taken part in the study declared that they do not have anything to disclose regarding funding from industry or conflict of interest with respect to this manuscript.

PII: S0168-8278(09)00373-0

doi: 10.1016/j.jhep.2009.04.021

Journal of Hepatology
Volume 51, Issue 3 , Pages 528-534 , September 2009

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