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

M. van der Stelt, C. Mazzola, G. Esposito, I. Matias, S. Petrosino, D. De Filippis, V. Micale, L. Steardo, F. Drago, T. Iuvone, V. Di Marzo
Cell. Mol. Life Sci.. 2006-05-29; 63(12): 1410-1424
DOI: 10.1007/s00018-006-6037-3

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1. Cell Mol Life Sci. 2006 Jun;63(12):1410-24. doi: 10.1007/s00018-006-6037-3.

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

van der Stelt M(1), Mazzola C, Esposito G, Matias I, Petrosino S, De Filippis D,
Micale V, Steardo L, Drago F, Iuvone T, Di Marzo V.

Author information:
(1)Endocannabinoid Research Group, Institute of Biomolecular Chemistry, C.N.R.
Pozzuoli, Naples, Italy.

We investigated the involvement of endocannabinoids in the control of neuronal
damage and memory retention loss in rodents treated with the beta-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 beta-amyloid neurotoxicity and its consequences.

DOI: 10.1007/s00018-006-6037-3
PMID: 16732431 [Indexed for MEDLINE]

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