Endocannabinoids and Notch-1 signalling in an in-vitro model of Alzheimer's disease and with normal aging

Abstract

Notch is a universal arbiter of cell fate decision during development and in the adult brain. Aberrant Notch signaling has recently emerged as a possible mechanism that underlies altered neurogenesis, cognitive impairments, learning and memory deficit in Alzheimer’s disease (AD). Hes1 and Hes5 are the Notch target genes and key players in maintaining neuronal stem cell pool that sub serves long-lasting neurogenesis. The neuroprotective effects of the endocannabinoids, Anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) against β-amyloid-induced neurodegeneration are emerging, in this study the influence of the endocannabinoids AEA and 2-AG on the Notch-1 pathway and on its regulators in an in-vitro model of AD was investigated since this may represent a novel neuroprotective target. Primary neuronal cultures prepared from neonatal rat cerebral cortices were treated with AEA (10nM) or 2-AG (10nM) in the presence or absence of Aβ1-42 for 6 and 24 hours.