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with CPO showed a significant increase in TNF-α    Administration of galantamine partially attenuates the
           levels early following treatment. However, while the   effects of chlorpyrifos oxon on Aβ peptide levels and amyloid
           TNF-α levels in the liver and blood returned to baseline   plaque load
           within several days, the levels in the brain remained   As a potential therapeutic approach, we determined
           elevated for up to 12 months. Finally, brain sections   the impact of galantamine (a competitive and
           from the APP mice treated with and without CPO     reversible cholinesterase inhibitor) that can protect
           during lactation were subject to immunohistochemistry   against organophosphorus insecticides  [Figure  10].
           for GFAP [Figure 7e]. As shown in figure, GFAP was
           significantly elevated in the CPO treated mice compared
           with the control animals.

           Furthermore, we analyzed the protein carbonyl content (a
           biomarker of reactive oxygen species) in the brain of the
           APP mice, and found that the level of oxidized proteins
           was significantly increased (> 50%) in mice treated with
           CPO than in the control APP mice [Figure 8].

           Administration  of  chlorpyrifos  oxon  decreases  brain
           neurotrophic factors
           To further characterize the changes in brain following
           treatment with CPO, APP mice were evaluated for
           neurotrophic factor levels  [Figure  9]. Following
           treatment with CPO, mice were examined for nerve
           growth factor, brain-derived neurotrophic factor, and   Figure 8: Protein carbonyl content in the brains of amyloid precursor protein
                                                              (APP) transgenic mice treated with and without chlorpyrifos oxon. Extracts
           neurotrophin-3 levels in the brain [Table 3]. As shown   from the brains of APP transgenic mice were analyzed for the level of oxidized
           in figure, all treatments significantly reduced the   proteins by OxiSelect and enzyme‑linked immunosorbent assay. Values are
                                                              expressed as mean ± standard error of the mean, n = 12 per group. *Statistically
           neurotrophic factor levels in the brain.           significant (P < 0.05)



















                          a                                       b




















                                            c
           Figure 9: Treatment of amyloid precursor protein (APP) mice with chlorpyrifos oxon (CPO) results in a decrease in neurotrophic factors. Brain nerve growth factor,
           brain‑derived neurotrophic factor and neurotrophin‑3  levels (panels a, b and c, respectively) were determined by enzyme‑linked immunosorbent assay in APP
           mice (control) and APP mice treated with CPO (CPO). Values are shown as the mean ± standard error of the mean, and n = 12. *Statistically significant (P < 0.05)


            38                                             Neuroimmunol Neuroinflammation | Volume 2 | Issue 1 | January 15, 2015
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