# Mitochondrial Ultrastructure, Fission Proteins, Activity, and Motor Dysfunctions in the Innovative Parkinson’s Disease Model Induced by Manganese Inhalation

## TL;DR

This study shows that manganese inhalation in mice causes mitochondrial and motor issues similar to Parkinson’s disease, making it a useful model for testing treatments.

## Contribution

The study demonstrates that a manganese-induced mouse model replicates key mitochondrial and motor features of Parkinson’s disease.

## Key findings

- Manganese inhalation caused fine motor deficits and mitochondrial structural changes in mice.
- Increased Drp1 and Fis1 levels and reduced complex I and IV activity were observed in the substantia nigra.
- The model shows progressive, bilateral mitochondrial and motor impairments resembling Parkinson’s disease.

## Abstract

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.