It has already been reported that cannabinoids are neuroprotective agents against excitotoxicity in vitro and increase after acute brain damage in vivo. This background prompted us to study the localization and expression of the calcium -binding protein calretinin in a condition similar to Alzheimer disease and its possible relationship with cannabinoids and their supposed protective role. We carried out quantitative analysis of the transient changes in calretinin expression shown by hybridochemistry within neuronal cell populations in the hippocampus of a beta amyloid-treated rat model of Alzheimer's disease and their correlation with endocannabinoid increase. Calretinin expression increases throughout the first week after cortical amyloid-beta peptide injection, and then decreases towards normal levels in the rat hippocampus during the following weeks, indicating that decreased calretinin gene expression may be associated with either increase of endocannabinoids or VDM11-induced accumulation of endocannabinoids. In contrast, SR1, an antagonist, which limits the cannabinoid effect by selective binding to the cannabinoid receptor CB1, up-regulates calretinin expression with respect to non-treated rats. This could mean that the SR1 endocannabinoid-blocking action through CB1 receptors, that are normally stimulated by endocannabinoids to inhibit calcium increase, might cause a higher calretinin expression. This would allow us to speculate on a possible reverse relationship between endocannabinoid and calretinin levels in the hippocampal calcium-homeostasis balance.
Keywords: Alzheimer disease; Amyloid beta peptide; Calretinin; Endocannabinoids; Hippocampus; In situ hybridization.
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