Neurogenesis and morphological-neural alterations closely related to amyloid β-peptide (25-35)-induced memory impairment in male rats.

Memory impairment by the Amyloid-β 25-35 (Aβ25-35 ) peptide in animal models has provided an understanding of the causes behind the similar deterioration that occurs in Alzheimer's disease. However, it is uncertain if a decrease of dendritic spines and neurogenesis conduces to cognitive impairment by an impairment in the retrieval of stored memory. The aim of this study was to evaluate the consequences of impairment on spatial memory caused by the administration of the Aβ25-35 peptide in the hippocampus, which is associated whit morphological changes and neurogenesis in the dentate gyrus (DG). The vehicle or Aβ25-35 peptide (0.1μg/μL) were bilaterally administered in the CA1 subfield of the rat hippocampus. The animals were tested for spatial learning and memory in the Morris Water Maze. In the day's 11, 18 and 32 after administration of the Aβ25-35 peptide were examined the morphological changes in the DG using a Golgi-Cox stain. In the day 32, the neurogenesis was evaluated by the immunoreactivity to 5-bromo-2'-deoxyuridine (BrdU; 100mg/kg, i.p.) that corresponding to cellular proliferation post damage, the neuronal specific nuclear protein (NeuN) and doublecortin (DCX). This study found a memory retrieval impairment occurring at day 17, a cognitive deficit which had increased significantly at day 31 after the administration of Aβ25-35 peptide. These results are related to morphological changes in the granular cells of the DG, such as a shorter dendritic length and a decrease in the number of dendritic spines. In neurogenesis, the total number of cells positive to BrdU, NeuN and DCX in the hippocampal granule cell layer was found to have declined in animals treated with Aβ25-35 . The results suggest that the Aβ25-35 peptide impairs memory retrieval by decreasing the number of dendritic spines and altering neurogenesis in the DG.