# Systematic Evaluation of a Mouse Model of Aging-Associated Parkinson’s Disease Induced with MPTP and D-Galactose

## TL;DR

This study creates a mouse model that mimics both motor and aging-related symptoms of Parkinson’s disease, offering a better tool for research.

## Contribution

A novel mouse model combining MPTP and D-galactose to replicate both motor and aging-related non-motor symptoms of PD is introduced.

## Key findings

- MPTP + D-galactose-treated mice showed motor impairments and cognitive deficits.
- D-galactose alone caused cognitive impairment without motor dysfunction.
- The model also induced bone loss, a common aging-related symptom.

## Abstract

In this study, a Parkinson’s disease (PD) mouse model combining 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine and D-galactose treatments is systematically evaluated. The model reproduces both motor symptoms and aging-related cognitive impairment and bone loss. The findings provide a comprehensive tool for studying the pathogenesis of PD and evaluating potential therapies.

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by motor dysfunction and non-motor symptoms, including cognitive decline. Animal models that replicate PD’s clinical features are essential for therapeutic research. The widely used subacute 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP)-induced mouse model effectively mimics motor deficits but fails to fully represent aging-related non-motor symptoms. In this study, we established an aging-associated PD mouse model by combining MPTP with D-galactose treatment. Compared to mice treated with MPTP alone, MPTP + D-galactose-treated mice exhibited typical motor impairments alongside cognitive deficits in the Morris water maze and Y-maze tests. D-galactose alone induced cognitive impairment without motor dysfunction. Pathological analysis showed that the MPTP + D-galactose treatment caused tyrosine hydroxylase-positive neuron loss similar to MPTP, while D-galactose did not damage these neurons. Additionally, Micro-CT revealed bone loss in both the MPTP + D-galactose and D-galactose groups. This model recapitulates both the motor and aging-related non-motor symptoms of PD, including cognitive impairment and bone loss, providing a more comprehensive tool for studying PD pathogenesis and evaluating potential therapies.