MPTP-treated Mice

Disease Simulated: Parkinson's disease (PD)

 

Disease Description

Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily affects motor function. It is characterized by the degeneration of dopamine-producing neurons in the brain, which leads to symptoms such as tremors, bradykinesia, rigidity, and postural instability. Non-motor symptoms can also manifest, including cognitive impairment, mood disorders, and sleep disturbances. Globally, it affects approximately 8.5 million individuals, predominantly within the elderly population [1-2].

Modeling Protocol

  • Model Construction: MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) was administered intraperitoneally to induce a Parkinson’s disease model. Various dosing regimens of MPTP have been employed to replicate different aspects of the disease. According to the literature, an acute administration regimen refers to multiple injections given within 24 hours. In contrast, a subacute or chronic administration regimen involves a single daily injection administered over several consecutive or non-consecutive days or weeks.

  • Treatments and Behavioral Assessments: MPTP was injected intraperitoneally for 12 days. At the time point of the sixth day, open field test, pole test, and rotarod test were measured.

Figure 1. Experimental timeline of the behavior tests, model procedures,  and treatment schedules. MPTP (22.5mg/kg) was administered intraperitoneally to an MPTP-sensitive strain (C57BL/6) for 12 days. L-DOPA (600ug/kg) or drug 1 (600ug/kg) were injected intravenously once every 3 days. The open field test, pole test, and forced rotarod test were measured at specific time points.

Validation Data

1. Behavior Test

Figure 2. Behavior tests comprised open field tests, pole tests, and forced rotarod tests at specific time points. The MPTP-induced PD model was successfully established through three behavioral assessments. Following drug administration, the symptoms of PD were significantly alleviated.

 

References
[1]Ascherio A, Schwarzschild MA. The epidemiology of Parkinson's disease: risk factors and prevention. Lancet Neurol. 2016 Nov;15(12):1257-1272.
[2]Vijiaratnam N, Simuni T, Bandmann O, Morris HR, Foltynie T. Progress towards therapies for disease modification in Parkinson's disease. Lancet Neurol. 2021 Jul;20(7):559-572.