Dichlorvos exerts its toxic effects in humans and animals by inhibiting neural acetylcholinesterase. Chronic low-level exposure to dichlorvos has been shown to result in inhibition of the mitochondrial complex I and cytochrome oxidase in rat brain, resulting in generation of reactive oxygen species (ROS). Enhanced ROS production leads to disruption of cellular antioxidant defense systems and release of cytochrome c (cyt c) from mitochondria to cytosol resulting in apoptotic cell death. MitoQ is an antioxidant, selectively targeted to mitochondria and protects it from oxidative damage and has been shown to decrease mitochondrial

Semaxanib molecular weight damage in various animal models of oxidative stress. We hypothesized that if oxidative damage to mitochondria does play a significant role in dichlorvos induced neurodegeneration, then MitoQ should ameliorate neuronal apoptosis. Administration of MitoQ (100 mu mol/kg body wt/day) reduced dichlorvos IWR-1 cost (6 mg/kg body wt/day) induced oxidative stress (decreased ROS production, increased MnSOD activity and glutathione levels) with decreased lipid peroxidation, protein and DNA oxidation. In addition,

MitoQ also suppressed DNA fragmentation, cyt c release and caspase-3 activity in dichlorvos treated rats compared to the control group. Further electron microscopic studies revealed that MitoQ attenuates dichlorvos induced mitochondrial swelling, loss of cristae and chromatin condensation. These results indicate that MitoQ may be beneficial against OP

(dichlorvos) induced neurodegeneration. (C) 2011 Elsevier Ltd. All rights reserved.”
“Synapsin Suplatast tosilate is an evolutionarily conserved, presynaptic vesicular phosphoprotein. Here, we ask where and how synapsin functions in associative behavioral plasticity. Upon loss or reduction of synapsin in a deletion mutant or via RNAi, respectively, Drosophila larvae are impaired in odor-sugar associative learning. Acute global expression of synapsin and local expression in only the mushroom body, a third-order “”cortical”" brain region, fully restores associative ability in the mutant. No rescue is found by synapsin expression in mushroom body input neurons or by expression excluding the mushroom bodies. On the molecular level, we find that a transgenically expressed synapsin with dysfunctional PKA-consensus sites cannot rescue the defect of the mutant in associative function, thus assigning synapsin as a behaviorally relevant effector of the AC-cAMP-PKA cascade. We therefore suggest that synapsin acts in associative memory trace formation in the mushroom bodies, as a downstream element of AC-cAMP-PKA signaling. These analyses provide a comprehensive chain of explanation from the molecular level to an associative behavioral change.”
“Zinc is known to exert antidepressant-like actions and to make the effects of some antidepressants more efficient in animal models of depression.