title: Cypermethrin alters the expression profile of mRNAs in the adult rat striatum: a putative mechanism of postnatal pre-exposure followed by adulthood re-exposure-enhanced neurodegeneration.
abstract: This study was undertaken to investigate the effect of cypermethrin on the expression patterns of mRNAs in the striatum of adulthood alone and postnatal pre-exposed followed by adulthood re-exposed rats using discover chips rat microarrays. The expression patterns of V-akt murine thymoma viral oncogene homolog 1, B-cell lymphoma 2 (BCL-2), BCL-2-associated X protein, caspase 1, caspase 9, death-associated protein 3 and interleukin-1β were validated by the qRT-PCR. The expressions of inducible nitric oxide synthase (iNOS) and major histocompatibility complex (MHC) II were assessed immunohistochemically; however, tumour protein p53 and cytochrome c (mitochondrial and cytosolic) expressions were checked at protein level by western blotting. Cypermethrin differentially regulated 65 transcripts at one or the other stage of exposure and 21 transcripts exhibited more pronounced alterations in the postnatal pre-exposed and adulthood re-challenged rats. The results of qRT-PCR were in accordance with the microarray observations and the expressions of iNOS, p53 and cytosolic cytochrome c and MHC II positivity were increased while the level of mitochondrial cytochrome c was reduced in adulthood treated animals. The effects were more pronounced in the postnatal pre-exposed followed by adulthood re-exposed rats. The results obtained thus suggest that multiple pathways are involved in the neurodegeneration as well as in enhancing the vulnerability of neurons in cypermethrin pre-exposed postnatal animals upon re-exposure during adulthood.
authors.affiliation: CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Post Box-80, Lucknow 226 001, Uttar Pradesh, India.
authors.forename: Manindra Nath
authors.initials: MN
authors.lastname: Tiwari
authors.forename: Anand Kumar
authors.initials: AK
authors.lastname: Singh
authors.forename: Sonal
authors.initials: S
authors.lastname: Agrawal
authors.forename: Satya Prakash
authors.initials: SP
authors.lastname: Gupta
authors.forename: Anurag
authors.initials: A
authors.lastname: Jyoti
authors.forename: Rishi
authors.initials: R
authors.lastname: Shanker
authors.forename: Om
authors.initials: O
authors.lastname: Prakash
authors.forename: Mahendra Pratap
authors.initials: MP
authors.lastname: Singh
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D003342:Corpus Striatum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011722:Pyrethrins / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D007306:Insecticides; D011722:Pyrethrins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C017160:cypermethrin; D045304:Cytochromes c