Histological and Memory Alterations in an Innovative Alzheimer’s Disease Animal Model by Vanadium Pentoxide Inhalation

• Published in: Journal of Alzheimer's disease 2024-01, Vol.99 (1), p.121-143
• Main Authors: Dorado-Martínez, Claudia, Montiel-Flores, Enrique, Ordoñez-Librado, Jose Luis, Gutierrez-Valdez, Ana Luisa, Garcia-Caballero, Cesar Alfonso, Sanchez-Betancourt, Javier, Reynoso-Erazo, Leonardo, Tron-Alvarez, Rocio, Rodríguez-Lara, Vianey, Avila-Costa, Maria Rosa
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Alzheimer Disease - chemically induced; Alzheimer Disease - pathology; Alzheimer's disease; Amygdala; Animal diseases; Animal models; Animals; Brain - drug effects; Brain - metabolism; Brain - pathology; Cell death; Cerebral amyloid angiopathy; Chronic exposure; Cognitive ability; Cytoskeleton; Deionization; Dendritic spines; Dendritic Spines - drug effects; Dendritic Spines - pathology; Disease Models, Animal; Endothelium; Golgi apparatus; Hippocampus; Inhalation; Male; Maze Learning - drug effects; Memory; Memory Disorders - chemically induced; Memory Disorders - pathology; Memory tasks; Neurodegenerative diseases; Neurofibrillary tangles; Neurofibrillary Tangles - drug effects; Neurofibrillary Tangles - pathology; Plaque, Amyloid - pathology; Pyramidal cells; Rats; Rats, Wistar; Respiration; Senile plaques; Spatial analysis; Spatial memory; Spatial Memory - drug effects; Spine; Subiculum; Tyrosine; Vanadium; Vanadium Compounds - pharmacology; Vanadium pentoxide; β-Amyloid
• ISSN: 1387-2877; 1875-8908; 1875-8908
• DOI: 10.3233/JAD-230818

Background: Previous work from our group has shown that chronic exposure to Vanadium pentoxide (V2O5) causes cytoskeletal alterations suggesting that V2O5 can interact with cytoskeletal proteins through polymerization and tyrosine phosphatases inhibition, causing Alzheimer’s disease (AD)-like hippocampal cell death. Objective: This work aims to characterize an innovative AD experimental model through chronic V2O5 inhalation, analyzing the spatial memory alterations and the presence of neurofibrillary tangles (NFTs), amyloid-β (Aβ) senile plaques, cerebral amyloid angiopathy, and dendritic spine loss in AD-related brain structures. Methods: 20 male Wistar rats were divided into control (deionized water) and experimental (0.02 M V2O5 1 h, 3/week for 6 months) groups (n = 10). The T-maze test was used to assess spatial memory once a month. After 6 months, histological alterations of the frontal and entorhinal cortices, CA1, subiculum, and amygdala were analyzed by performing Congo red, Bielschowsky, and Golgi impregnation. Results: Cognitive results in the T-maze showed memory impairment from the third month of V2O5 inhalation. We also noted NFTs, Aβ plaque accumulation in the vascular endothelium and pyramidal neurons, dendritic spine, and neuronal loss in all the analyzed structures, CA1 being the most affected. Conclusions: This model characterizes neurodegenerative changes specific to AD. Our model is compatible with Braak AD stage IV, which represents a moment where it is feasible to propose therapies that have a positive impact on stopping neuronal damage.