MitoNEET loss impacts motor and cognitive function differentially in male and female mice

Presenters/Authors(s)

Katrina Hernandez, Kaitlynn Smith, Werner Geldenhuys, Gina Wilson

Abstract or Description

MitoNEET is a mitochondrial outer membrane protein that has emerged as a key player in cellular iron metabolism and redox regulation. It is suggested to be involved in neurodegenerative diseases, but we do not fully understand the mechanisms underlying this. However, mice lacking mitoNEET experience cell loss, particularly in cholinergic and dopaminergic populations, which has direct implications for cognitive and motor functions. This study aims to elucidate the impact of mitoNEET loss on motor and cognitive behavior in male and female mice 2-17 months of age, and simultaneously address potential confounds regarding motor defects on performance in cognitive tasks. Using a genetic mouse model to knockout mitoNEET globally, we assessed resulting phenotypes across a spectrum of behavioral tasks. For motor function, we employed the wire hang test, rotarod test, and ex vivo muscle testing using an isolated muscle assay. Cognitive functions were evaluated using the puzzle maze for spatial learning and memory. Our results indicate that mitoNEET deficiency exacerbates age-related declines in both motor and cognitive functions, with younger mice displaying minor deficits that progressively worsen with age. Additionally, we identified variations in muscle strength and function that should guide researchers in selecting appropriate ages and cognitive tasks for this transgenic strain. By distinguishing the onset and progression of motor versus cognitive impairments, we aim to better understand the progression of behavioral decline. These findings highlight the critical role of mitoNEET in maintaining neuronal health and underscore its potential as a therapeutic target for mitigating age-associated motor and cognitive decline.