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Increase of striatal dopamine turnover by stress in MPTP-treated mice
K Urakami1, N Masaki, K Shimoda
1Division of Neurology, Tottori University School of Medicine, Yonago, Japan.
Abstract:
The characteristics of motor function and brain dopamine (DA) metabolism in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice after immersion immobilization stress were investigated. There was no significant difference in locomotor activities between MPTP-treated and saline-treated mice, but locomotor activities of MPTP-treated mice after stress decreased more remarkably than those of saline-treated mice. Immediately after stress, striatal DA concentrations of MPTP-treated mice were significantly lower than those of saline-treated mice. Striatal DA levels improved when 24 h passed after stress. The striatal and cortical (DOPAC + HVA)/DA ratios of MPTP-and stress-treated mice was significantly higher than that of saline-and stress-treated mice. It is due to the decreased DA level and the enhancement of DA turnover that MPTP-treated mice became remarkably akinetic after stress, and that L-DOPA therapy is not effective when the symptoms in patients with Parkinson's disease worsen due to stress.
Insights
Stress significantly worsens motor function in mice with Parkinson
Area of Science:
- Neuroscience
- Pharmacology
- Stress Research
Background:
- Parkinson's disease is characterized by motor deficits and dopamine (DA) deficiency.
- Stress is known to exacerbate symptoms in Parkinson's disease patients.
- The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model mimics Parkinson's disease pathology.
Purpose of the Study:
- To investigate the impact of immersion immobilization stress on motor function and dopamine metabolism in MPTP-treated mice.
- To understand the neurochemical basis for stress-induced motor decline in Parkinson's disease models.
- To explore the implications for L-DOPA therapy efficacy during stress.
Main Methods:
- MPTP treatment to induce Parkinson's-like symptoms in mice.
- Immersion immobilization stress protocol.
- Assessment of locomotor activity.
- Measurement of striatal dopamine (DA) and its metabolites (DOPAC, HVA) using biochemical assays.
Main Results:
- MPTP-treated mice showed a more significant decrease in locomotor activity after stress compared to controls.
- Striatal DA levels were significantly reduced immediately after stress in MPTP-treated mice.
- Increased (DOPAC + HVA)/DA ratios in striatum and cortex indicated enhanced DA turnover post-stress.
- DA levels partially recovered 24 hours after stress.
Conclusions:
- Stress exacerbates motor impairment in the MPTP mouse model by reducing dopamine levels and increasing dopamine turnover.
- These findings suggest that stress-induced neurochemical changes may contribute to the reduced effectiveness of L-DOPA therapy in advanced Parkinson's disease.
- Further research is needed to explore therapeutic strategies mitigating stress effects in Parkinson's disease.