104 | Longitudinal characterization of morphological and behavioral alterations in the streptozotocin (STZ)-induced sporadic Alzheimer’s disease (AD) model

Cognition, Behavior, and Memory

Author: Jazmín Fleitas | Email: jazzyfleitas@gmail.com

Rossana Cabral , Sofía Niño-Rivero , Lucía Alcalde , Jazmín Fleitas , Pablo Galeano , Patricia Lagos

1° Unidad Académica de Fisiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
2° Laboratory of Brain Aging and Neurodegeneration, Fundación Instituto Leloir (IIBBA-CONICET), Ciudad Autónoma de Buenos Aires, Argentina.

In this work, we performed a longitudinal characterization of morphological and behavioral alterations in the STZ-induced AD model. To this end, male rats were administered intracerebroventricularly with STZ, or vehicle, and 15, 30, 60, 90 and 120 days post-administration were subjected to the Novel Object Recognition (NOR) test and to the modified Elevated Plus Maze (mEPM) test, followed by immunohistochemistry studies. Glycemia was not altered at any time point. At 15 days, STZ-treated rats showed a significant decrease number in NeuN-positive neurons and an increased density of GFAP-positive astrocytes in parietal cortex and hippocampus. Also, the number of ChAT-positive neurons was decreased in cortex while cholinergic fiber density was decreased in hippocampus. These morphological modifications persisted across all the time points studied. Regarding behavioral performance, STZ-rats showed cognitive deficits in the NOR at 90 and 120 days post-STZ administration while no alterations were observed in the mEPM test at any time point. Based on these results, we could define, in this AD model, two phases: an early one (15, 30 and 60 days post-STZ administration) characterized by morphological alterations and a late one (90 and 120 days post-STZ administration) when cognitive deficits appear. This temporal pattern recapitulates what has been observed in AD, where pathophysiological changes begin years before cognitive deficits are manifested.