Aβ40 Oligomers Promote Survival and Early Neuronal Differentiation of Dentate Gyrus-Isolated Precursor Cells Through Activation of the Akt Signaling Pathway

The amyloid beta-peptide (A beta) is the low-abundance product of amyloid precursor protein (APP), which is produced lifelong in the healthy brain. The functional properties of A beta 40 and A beta 42 peptides have not been completely elucidated to date. Although, several studies suggest that these peptides have a number of neurotrophic and neurotoxic properties, respectively. Interestingly, low concentrations of A beta 40 and A beta 42 regulate synaptic plasticity and improve cognitive functions, whereas the accumulation of A beta 42, coupled with the effects of age, can cause dysregulation of synaptic function, as is shown in Alzheimer's disease. Additionally, several studies suggest that both peptides, A beta 40 and A beta 42, are involved in neurogenic processes; however, these results are still controversial. Moreover, existing data indicate a direct relationship between the physicochemical characteristics of the peptides and their effects. Herein, we evaluated the effect of A beta 40 oligomers on hippocampal precursor cells isolated from the dentate gyrus of adult female C57Bl6 mice (mADGPCs). To this end, mADGPCs were treated with nanomolar and micromolar range concentrations of oligomeric forms of A beta 40 for 24, 48, and 72 h to evaluate their effects on several events in the neurogenic process in vitro, including viability, proliferation, and early differentiation. The results indicate that A beta 40 favors mADGPC proliferation, survival, and neuronal differentiation following a mechanism that involves activation of the Akt signaling pathway. Thus, this study provides evidence about the positive effects of A beta 40 oligomers on the neurogenic process in adult mouse hippocampal precursor cells in vitro.