Neurogenesis in a rat model of sporadic Alzheimer's disease
Sara L. Paulo1,2,, , Rui S. Rodrigues1,2, Liana Shvachiy3, Filipa F. Ribeiro1,2, Susana Solá4, Ana M. Sebastião1,2, Sara Xapelli1,2
1 Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
2 Instituto de Medicina Molecular (iMM), Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
3 Cardiovascular Autonomic Function (CAF) lab, Cardiovascular Center of the University of Lisbon (CCUL), Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
4 Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal

Aim: Characterize adult hippocampal neurogenesis in a rat model of the initial stages of sporadic Alzheimer's disease (AD).

Introduction: Sporadic late-onset AD is the most common cause of dementia, that can be characterized by a progressive cognitive decline, with a noteworthy episodic long-term memory impairment at early stages, accompanied by an excess accumulation of amyloid beta (Aβ) peptide in the brain. Present treatment options are very limited, so understanding AD pathophysiology is essential for exploring efficient therapies. Adult hippocampal neurogenesis is thought to play a crucial role in hippocampus-dependent cognitive abilities, namely learning/memory, although how this process is modulated in AD remains unclear.

Methods: An Aβ1–42 peptide solution was intracerebroventricularly injected into the rats’ lateral ventricle (the same volume of vehicle was injected to controls). Moreover, rats were injected with 5-bromo-2′-deoxyuridine (BrdU) intraperitoneally to study cell proliferation and differentiation. Two weeks after Aβ1-42 injection, the open field (OF) test and the novel object recognition (NOR) test were performed. Further behaviour tests are currently being performed, including the elevated plus maze (EPM), the Y-maze forced alternation test, and the Morris water maze (MWM) test. Focusing on the dentate gyrus, immunohistochemical analysis is presently being performed to investigate cell proliferation, neuronal differentiation and neuroblast/neuron morphology. Additionally, the presence of Aβ1–42 monomers and oligomers will be assessed by western-blot and the eventual occurrence of Aβ1–42 aggregates by histology.

Results: Our results show that the Aβ1–42 injection did not affect locomotor activity, as assessed by the OF test. Furthermore, this injection did not affect exploratory drive or episodic long-term memory performance, as indicated by the NOR test.

Conclusion: Since the NOR test is dependent from several brain regions besides the hippocampus that might not be affected in our model, additional behaviour tests as well as cellular and molecular analysis are needed to further characterize this model.

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