Cellular and Molecular Life Sciences CMLS

, Volume 63, Issue 12, pp 1410–1424

Endocannabinoids and β-amyloid-induced neurotoxicity in vivo: effect of pharmacological elevation of endocannabinoid levels

Authors

  • M. van der Stelt
    • Endocannabinoid Research GroupInstitute of Biomolecular Chemistry
    • NV Organon
  • C. Mazzola
    • Department of Experimental and Clinical PharmacologyUniversity of Catania Medical School
  • G. Esposito
    • Department of Experimental PharmacologyUniversity of Naples Federico II
  • I. Matias
    • Endocannabinoid Research GroupInstitute of Biomolecular Chemistry
  • S. Petrosino
    • Endocannabinoid Research GroupInstitute of Biomolecular Chemistry
  • D. De Filippis
    • Department of Experimental PharmacologyUniversity of Naples Federico II
  • V. Micale
    • Department of Experimental and Clinical PharmacologyUniversity of Catania Medical School
  • L. Steardo
    • Department of Human Physiology and Pharmacology‘V. Espamer’, University of Rome ‘La Sapienza’
  • F. Drago
    • Department of Experimental and Clinical PharmacologyUniversity of Catania Medical School
  • T. Iuvone
    • Department of Experimental PharmacologyUniversity of Naples Federico II
    • Endocannabinoid Research GroupInstitute of Biomolecular Chemistry
Research Article

DOI: 10.1007/s00018-006-6037-3

Cite this article as:
van der Stelt, M., Mazzola, C., Esposito, G. et al. Cell. Mol. Life Sci. (2006) 63: 1410. doi:10.1007/s00018-006-6037-3

Abstract.

We investigated the involvement of endocannabinoids in the control of neuronal damage and memory retention loss in rodents treated with the β-amyloid peptide (1–42) (BAP). Twelve days after stereotaxic injection of BAP into the rat cortex, and concomitant with the appearance in the hippocampus of markers of neuronal damage, 2-arachidonoyl glycerol, but not anandamide, levels were enhanced in the hippocampus. VDM-11 (5 mg/kg, i.p.), an inhibitor of endocannabinoid cellular reuptake, significantly enhanced rat hippocampal and mouse brain endocannabinoid levels when administered sub-chronically starting either 3 or 7 days after BAP injection and until the 12–14th day. VDM-11 concomitantly reversed hippocampal damage in rats, and loss of memory retention in the passive avoidance test in mice, but only when administered from the 3rd day after BAP injection. We suggest that early, as opposed to late, pharmacological enhancement of brain endocannabinoid levels might protect against β-amyloid neurotoxicity and its consequences.

Keywords.

Anandamide2-arachidonoyl glycerolcannabinoidmemoryreceptorneuroprotectionapoptosis

Copyright information

© Birkhäuser Verlag, Basel 2006