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Alterations of somatostatin and its modulation by levodopa in MPTP-treated mouse brain
1Department of Neurochemistry, Okayama University Medical School, Japan.
Abstract:
We examined the changes in the concentrations of neuropeptides in various regions of the mouse brain 1, 2 or 6 weeks after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment (30 mg/kg i.p. twice/day for 5 days) and further examined the effects of levodopa injections (200 mg/kg i.p.) for 14 days starting 4 weeks after MPTP treatment on regional somatostatin (SRIF) concentrations. Substance P, cholecystokinin-octapeptide and thyrotropin-releasing hormone did not show any significant changes up to 6 weeks after MPTP treatment, whereas the SRIF concentration increased 1 week after MPTP treatment but decreased thereafter, showing a marked decrease in the striatum and hippocampus after 6 weeks. In the striatum, the decreased concentration of SRIF recovered to the normal level with levodopa injections. This SRIF depletion could be a change secondary to dopamine depletion. On the other hand, in the cerebral cortex, while showing no change in the SRIF concentration after MPTP treatment, the concentration decreased significantly with levodopa injections. In the hippocampus, the decreased SRIF levels were still low after levodopa treatment. Since it has been reported that SRIF concentrations are significantly reduced in the frontal cortex and hippocampus of demented parkinsonians and patients with senile dementia of the Alzheimer type and that levodopa treatment induced various psychiatric side effects, the results of the present study suggest some relationship among levodopa treatment, SRIF depletion and the demented state.
Insights
MPTP-induced brain changes in mice show altered somatostatin (SRIF) levels, particularly in the striatum and hippocampus. Levodopa partially restored SRIF in the striatum but decreased it in the cortex, suggesting a link to dementia.
Area of Science:
- Neuroscience
- Neuropharmacology
Background:
- 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin used to model Parkinson's disease.
- Neuropeptides play crucial roles in brain function, and their dysregulation is implicated in neurological disorders.
Purpose of the Study:
- To investigate the impact of MPTP treatment and subsequent levodopa administration on regional neuropeptide concentrations in the mouse brain.
- To explore the relationship between somatostatin (SRIF) levels, dopamine depletion, levodopa treatment, and potential cognitive decline.
Main Methods:
- Mice were treated with MPTP, and neuropeptide concentrations (Substance P, cholecystokinin-octapeptide, thyrotropin-releasing hormone, and SRIF) were measured in various brain regions at 1, 2, and 6 weeks post-treatment.
- Following MPTP exposure, a subset of mice received levodopa treatment, and regional SRIF concentrations were reassessed.
Main Results:
- MPTP treatment did not significantly alter Substance P, cholecystokinin-octapeptide, or thyrotropin-releasing hormone levels.
- SRIF concentrations initially increased post-MPTP but decreased significantly in the striatum and hippocampus by 6 weeks.
- Levodopa restored SRIF in the striatum but decreased it in the cerebral cortex, while hippocampal SRIF remained low.
Conclusions:
- MPTP-induced SRIF depletion in the striatum and hippocampus may be secondary to dopamine loss.
- Levodopa's differential effects on regional SRIF, particularly the decrease in the cortex, warrant further investigation regarding psychiatric side effects and dementia.
- The findings suggest a complex interplay between levodopa, SRIF modulation, and the potential development of cognitive impairments in parkinsonian models.