Interleukine-1beta and interleukine-6 levels in striatum and other brain structures after MPTP treatment: influence of behavioral lateralization.
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.
Shen
Yan-Qin
YQ
Department of Microbiology and Immunology, Shantou University Medical College, 12 Raoping Road, Shantou, Guangdong 515031, P.R. China.
Hebert
Guillaum
G
Lin
Ling-Yun
LY
Luo
Yan-Ling
YL
Moze
Elizabeth
E
Li
Kang-Sheng
KS
Neveu
Pierre J
PJ
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005247:Feeding Behavior / Q000187:drug effects*; D007839:Functional Laterality / Q000187:drug effects*; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D020267:MPTP Poisoning; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D015259:Dopamine Agents; D007375:Interleukin-1; D015850:Interleukin-6; D015102:3,4-Dihydroxyphenylacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine