No abstract

Indoxacarb and metaflumizone belong to a relatively new class of sodium channel blocker insecticides (SCBIs). Due to intensive use of indoxacarb, field-evolved indoxacarb resistance has been reported in several lepidopteran pests including the diamondback moth, Plutella xylostella, a serious pest of cruciferous crops. In particular, the BY12 population of P. xylostella, collected from Baiyun, Guangdong province of China in 2012, was 750-fold more resistant to indoxacarb and 70-fold more resistant to metaflumizone compared with the susceptible Roth strain. Comparison of cDNA sequences encoding the sodium channel genes of Roth and BY12 revealed two point mutations (F1845Y and V1848I) in the 6th segment of domain IV of the PxNav protein in the BY population. Both mutations are located within a highly conserved sequence region that is predicted to be involved in the binding sites of local anesthetics and SCBIs based on mammalian sodium channels. A significant correlation was observed among ten field-collected populations between the mutant allele (Y1845 or I1848) frequencies (1.7% to 52.5%) and resistance levels to both indoxacarb (34- to 870-fold) and metaflumizone (1- to 70-fold). The two mutant alleles were never found to co-exist in the same allele of PxNav, suggesting that they arose independently. This is the first time that sodium channel mutations have been associated with high levels of resistance to SCBIs. F1845Y and V1848I are molecular markers for resistance monitoring in the diamondback moth and possibly other insect pest species.

No abstract

Oxidative stress and neuroinflammation are early events associated with dopaminergic neuronal degeneration in Parkinson's disease (PD). Previous studies indicated that electroacupuncture (EA) stimulation is effective in protecting dopaminergic neurons from degeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In this study, we further characterized the effect of EA on MPTP-induced oxidative responses in the mouse dopamine system. We found that subacute administration of MPTP enhanced lipid and protein oxidation and reduced expression of endogenous antioxidant enzymes (such as superoxide dismutase and catalase) in the striatum. MPTP also reduced expression of an antioxidant transcription factor, nuclear factor-E2-related factor-2 (Nrf2), and Nrf2-regulated antioxidant enzymes (nicotinamide adenine dinucleotide phosphate quinone oxidoreductase-1 and heme oxygenase-1) in the striatum and/or midbrain. Using human placental alkaline phosphatase (hPAP) as a reporter of Nrf2-regulated gene expression in hPAP transgenic mice, we found that MPTP suppressed hPAP expression in the striatum and midbrain. Application of EA at an effective frequency (100 Hz) was sufficient to reverse these changes induced by MPTP. In addition, EA reduced microglia activation and astrogliosis in the striatum and midbrain, increased tyrosine hydroxylase levels in the striatum, and improved vertical movement in MPTP mice. These results provide further evidence supporting that EA produces a series of anti-oxidative effects that effectively counteract with the oxidative stress in the nigrostriatal dopamine system induced by MPTP in a mouse model of PD.