Late-onset sporadic Alzheimers disease (AD) is the most common neurodegenerative disorder worldwide, yet present treatment options are still very limited. Modulating adult hippocampal neurogenesis (AHN) as a potential therapeutic target for AD has been explored. However, how the process is regulated in AD remains unclear, as studies show controversial results, arising mainly from models of the familial form. Hence, in the present work, aiming at characterizing AHN in a model of the initial stages of sporadic AD, male Wistar rats were intracerebroventricularly injected with an Aβ1-42 peptide solution. Behaviour tests carried out two weeks after the injection unexpectedly revealed no impact on locomotor activity (open field), anxious-related behaviour (elevated plus maze) or learning and memory performance (novel object recognition, Y-maze, Morris water maze). Assessment of neurogenic markers one month after 5-bromo-2-deoxyuridine administration showed abnormally enhanced dendritic morphology of immature neurons in the dentate gyrus, while proliferation and neuronal differentiation were preserved. As brain-derived neurotrophic factor signalling has been shown to be compromised in the presence of Aβ due to the cleavage of TrkB full-length receptors, the levels of these receptors isoforms were evaluated. No evidence of cleavage was found at 3 or 14 days post-Aβ-infusion. Consistently, the levels of Aβ1-42 species were unaltered at these timepoints, as was the number of astrocytes and microglia. Overall, although this model has been previously described as a model of sporadic AD, the expected behavioural, cellular or molecular phenotypes were not observed, further highlighting the variability of results found in the literature.
Author and article information
] Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de
Lisboa, Lisboa, Portugal; Instituto de Medicina Molecular João Lobo Antunes (iMM),
Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
] Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade
de Lisboa, Lisboa, Portugal.
This work has been published open access under Creative Commons Attribution License
CC BY 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided
can be found at
Data availability: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.