Nicotine- and caffeine-mediated changes in gene expression patterns of MPTP-lesioned mouse striatum: Implications in neuroprotection mechanism.
Exposure to 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) induces dopaminergic neurodegeneration in the nigrostriatal pathway and nicotine and caffeine ameliorate neurodegenerative changes in MPTP-lesioned mouse model of Parkinson's disease (PD). The present study was undertaken to investigate the effect of nicotine and caffeine on the expression patterns of genes in the striatum of control and MPTP-treated mice to identify the differentially expressed transcripts and to assess their possible implications in neuroprotection. Mice were treated intraperitoneally with caffeine (20mg/kg) or nicotine (1mg/kg), daily, for the first 8 weeks followed by MPTP (20mg/kg) co-treatment for further 4 weeks along with respective controls. RNA was isolated from the striatum of control and treated mice; reverse transcribed separately into labeled cDNA and a mixture of equal quantities of labeled cDNA was hybridized with mouse 15k array. The expression levels of toll-interleukin-1 receptor domain-containing adaptor protein, nuclear protein-1, cathepsin B, interleukin-4 receptor, caspase 9, complement component-1, heat shock protein-1 and cytochrome c-oxidase-VIIc were validated by quantitative real-time polymerase chain reaction (qRT-PCR). MPTP differentially regulated the expression of many genes involved in apoptotic cell death, oxidative stress, cell cycle regulation, protein modification and mitochondrial dysfunction. The expression patterns of many of these transcripts were significantly restored in caffeine- and nicotine-treated mice. The results demonstrate the involvement of multiple molecular events in MPTP-induced toxicity and nicotine or caffeine-mediated neuroprotection.
Singh
Kavita
K
Indian Institute of Toxicology Research, Lucknow, India.
Singh
Seema
S
Singhal
Naveen Kumar
NK
Sharma
Amit
A
Parmar
Devendra
D
Singh
Mahendra Pratap
MP
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001483:Base Sequence; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D007274:Injections, Intraperitoneal; D020267:MPTP Poisoning / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017472:Receptors, Interleukin-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D018696:Neuroprotective Agents; D009498:Neurotoxins; D017472:Receptors, Interleukin-1; D002110:Caffeine; D009538:Nicotine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine