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

Article type: Research Article

Authors: Dorado-Martínez, Claudia^a | Montiel-Flores, Enrique^a | Ordoñez-Librado, Jose Luis^a | Gutierrez-Valdez, Ana Luisa^a | Garcia-Caballero, Cesar Alfonso^a | Sanchez-Betancourt, Javier^d | Reynoso-Erazo, Leonardo^b | Tron-Alvarez, Rocio^b | Rodríguez-Lara, Vianey^c | Avila-Costa, Maria Rosa^{a; *}

Affiliations: [a] Neuromorphology Lab, Facultad de Estudios Superiores Iztacala, UNAM, Los Reyes Iztacala, Tlalnepantla, Edo. Mex., Mexico | [b] Health Education Project, Facultad de Estudios Superiores Iztacala, UNAM, Mexico City, Mexico | [c] Department of Cell and Tissue Biology, Faculty of Medicine, UNAM, Mexico City, Mexico | [d] FCAyS, UABC, Ensenada, Baja California, México

Correspondence: [*] Correspondence to: Maria Rosa Avila-Costa, Facultad de Estudios Superiores Iztacala, UNAM, Av. de los Barrios 1, Los Reyes Iztacala, Tlalnepantla, Edo. Mex. 54090, Mexico. Tel.: +5554330676; E-mail: [email protected].

Abstract: 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.

Keywords: Alzheimer’s disease experimental model, Aβ plaques, cell death, dendritic spine loss, inhaled exposure, neurofibrillary tangles, Vanadium pentoxide

DOI: 10.3233/JAD-230818

Journal: Journal of Alzheimer's Disease, vol. 99, no. 1, pp. 121-143, 2024