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Interleukine-1beta and interleukine-6 levels in striatum and other brain structures after MPTP treatment: influence
Yan-Qin Shen1, Guillaum Hebert, Ling-Yun Lin
1Department of Microbiology and Immunology, Shantou University Medical College, 12 Raoping Road, Shantou, Guangdong 515031, P.R. China.
Abstract:
MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induces diminution of the dopamine in nigrostriatal pathway and cognitive deficits in mice. MPTP treatment also increases pro-inflammatory cytokine production in substantia nigra and striatum. Since, pro-inflammatory cytokines influence striatal dopamine content and provoke cognitive impairments, the cognitive defects induced by MPTP may be partly due to brain cytokine induction in other structures than nigrostriatal pathway. Furthermore, behavioral lateralization, as assessed by paw preference, influences cytokine production at the periphery and in the central nervous system. Behavioral lateralization may thus influence brain cytokine levels after MPTP. In order to address these issues, mice selected for paw preference were injected with 25 mg/kg MPTP i.p. for five consecutive days after which striatal dopamine and DOPAC contents were measured by HPLC and IL-1beta and IL-6 quantified by ELISA in the striatum, cerebral cortex, hippocampus and hypothalamus. The results showed that MPTP treatment induced dramatic loss of DA in striatum, simultaneously, IL-6 levels decreased in the striatum and increased in hippocampus and hypothalamus, while IL-1beta levels decreased in the striatum, cerebral cortex and hippocampus. Interestingly, striatal dopamine turnover under basal conditions as well as striatal IL-1beta and IL-6 levels under basal conditions and after MPTP depended on behavioral lateralization. Left pawed mice showed a higher decrease in dopamine turnover and lower cytokine levels as compared to right pawed animals. Behavioral lateralization also influenced IL-6 hippocampal levels under basal conditions and IL-1beta cortical levels after MPTP. From these results, it can be concluded that MPTP-induced cognitive defects are accompanied by an alteration of pro-inflammatory cytokine levels in brain structures other than those involved in the nigrostriatal pathway. In addition, MPTP-induced dopamine decrease is influenced by behavioral lateralization, possibly through an effect on brain cytokine levels.
Insights
MPTP causes dopamine loss and cognitive deficits, partly due to altered brain cytokine levels beyond the nigrostriatal pathway. Behavioral lateralization influences these MPTP effects on dopamine and cytokines.
Area of Science:
- Neuroscience
- Immunology
- Behavioral Science
Background:
- MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induces dopamine depletion and cognitive deficits.
- MPTP increases pro-inflammatory cytokines in the substantia nigra and striatum.
- Cytokines can influence dopamine levels and cognitive function, suggesting broader brain involvement.
Purpose of the Study:
- To investigate if MPTP-induced cognitive defects involve cytokine changes in brain regions outside the nigrostriatal pathway.
- To determine the influence of behavioral lateralization on MPTP-induced dopamine changes and cytokine production.
Main Methods:
- Mice selected for paw preference were administered MPTP (25 mg/kg i.p. for 5 days).
- Striatal dopamine and DOPAC were measured using HPLC.
- IL-1beta and IL-6 levels were quantified by ELISA in the striatum, cerebral cortex, hippocampus, and hypothalamus.
Main Results:
- MPTP caused significant dopamine loss in the striatum.
- MPTP altered IL-6 and IL-1beta levels across brain regions, with decreases in the striatum and increases/decreases in other areas.
- Behavioral lateralization (paw preference) affected basal dopamine turnover and cytokine levels, as well as MPTP's impact on these measures.
Conclusions:
- MPTP-induced cognitive deficits are associated with altered pro-inflammatory cytokine levels in brain areas beyond the nigrostriatal pathway.
- MPTP-induced dopamine reduction is modulated by behavioral lateralization, potentially via effects on brain cytokine levels.

