Neurogenesis and morphological-neural alterations closely related to amyloid β-peptide (25-35)-induced memory impairment in male rats
Eleazar Ramírez1, Liliana Mendieta1, Gonzalo Flores2
1Laboratorio de Neurofarmacología edificio 105 C - FCQ, BUAP, Puebla, Mexico.
Abstract:
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.
Insights
Amyloid-β 25-35 peptide impairs memory retrieval by reducing dendritic spines and neurogenesis in the hippocampus. This study investigated the peptide
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Amyloid-β 25-35 (Aβ$_{25-35}$) peptide administration in animal models mimics Alzheimer's disease memory deficits.
- The role of dendritic spine loss and reduced neurogenesis in Aβ$_{25-35}$-induced cognitive impairment remains unclear.
Purpose of the Study:
- To investigate the impact of hippocampal Aβ$_{25-35}$ administration on spatial memory retrieval.
- To assess associated morphological changes and neurogenesis alterations in the dentate gyrus (DG).
Main Methods:
- Rats received bilateral intrahippocampal administration of Aβ$_{25-35}$ or vehicle.
- Spatial memory was evaluated using the Morris Water Maze.
- Hippocampal DG morphology and neurogenesis were assessed using Golgi-Cox staining, BrdU, NeuN, and DCX immunoreactivity at various time points.
Main Results:
- Aβ$_{25-35}$ administration led to significant memory retrieval impairment by day 17, worsening by day 31.
- Morphological analysis revealed decreased dendritic length and spine density in DG granular cells.
- Neurogenesis markers (BrdU, NeuN, DCX) were significantly reduced in the DG granule cell layer.
Conclusions:
- Aβ$_{25-35}$ peptide induces spatial memory retrieval deficits.
- These deficits are associated with reduced dendritic spine density and impaired neurogenesis in the dentate gyrus.
- The findings suggest Aβ$_{25-35}$ disrupts memory retrieval through structural and neurogenic alterations in the hippocampus.
