Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, yet its pathogenic mechanisms remain incompletely understood, highlighting the need for reliable experimental models. We previously developed a murine model based on inhalation of a manganese mixture (MnCl₂ and Mn(OAc)₃), which reproduces dopaminergic neuron loss in the substantia nigra pars compacta (SNc) and motor impairment. However, its capacity to mimic mitochondrial dysfunction, a key mechanism in PD, had not been explored. This study evaluated mitochondrial ultrastructure, fission and fusion proteins, and the activity of electron transport chain complexes I and IV, alongside fine motor performance. Forty male CD1 mice were divided into control (deionized water) and manganese-exposed groups (0.04 M MnCl₂ + 0.02 M Mn(OAc)₃), inhaled for 1 h twice weekly over five months. Manganese inhalation induced significant fine motor deficits, increased mitochondrial number with reduced area and circularity, and disorganized cristae. Drp1 and Fis1 levels were elevated, accompanied by decreased activity of complexes I and IV, predominantly in the SNc. These findings demonstrate that this progressive, bilateral model reproduces mitochondrial and motor alterations resembling those observed in PD, supporting its utility for testing mitochondria-targeted therapeutic strategies.

Chronic exposure to vanadium pentoxide (V₂O₅) has been linked to neuronal damage equivalent to that found in Alzheimer’s disease (AD). Prior research has indicated that chronic inhalation of V₂O₅ results in cellular and behavioral changes akin to those observed in AD. A total of 40 male Wistar rats were categorized into two control groups and two experimental groups for the study. The experimental inhaled V₂O₅ for 6 months; after 6 months, two groups (control and exposed) were left in a 6-month recovery phase. All groups were evaluated monthly for 6 or 12 months in a spatial memory test. To measure histological alterations, hippocampus CA1, entorhinal and frontal cortices, amygdala, and subiculum underwent Congo red or argentic Bielschowsky impregnation and were analyzed. Memory results show impairment since the third month. The group left in recovery did not show improvement. Chronic V₂O₅ inhalation is an AD model that causes irreversible alterations in spatial memory, accumulation of Aβ plaques, accumulation of NFTs, and loss of dendritic spines with no recovery. These alterations are not reversible after 6 months, indicating that the damage increases once the neurodegenerative process is established and the homeostasis is broken. This model characterizes sporadic AD, representing more than 95% of cases.