The Neurotoxicity Mechanisms Of Fenpropathrin On The Degeneration Of Neurons

Parkinson’s disease(PD)is the second common chronic neurodegenerative disease that is often manifested by degeneration of dopaminergic(DA)neurons in the substantia nigra pars compacta(SNpc)of the midbrain which result in the significantly decreased of DA content in the striatum(STR).Thus,the clinical symptoms of PD include resting tremor,bradykinesia,rigidity,postural instability and the pathological features are mainly degeneration of dopaminergic neuron and the formation of Lewy bodies containing alpha-synuclein(á-Syn)in the neurons.Both studies experimental zoology and cytobiology have shown that oxidative stress,neuroinflammation,glutamate excitotoxicity,and mitochondrial dysfunction are involved in the pathogenesis of PD.The studies of etiological have shown that age,genetics and environmental factors are important risk factors for PD.Though the environmental factors are the most common with them,but it can be easy to devoid than others.Therefore,studying the effects of environmental toxins on PD is of great significance in the prevention and treatment of Parkinson’s disease.A large number of evidences have shown that pyrethroid(pyr)can impair the DA system of animal,though it is not confirm about that pyr induced the PD.Thus,pyr is considered an important risk factors for PD.The mechanism of damaged DA mediated by pyr is unclear and still needs to be further researched.Our partner found that the higher incidence of PD may be associated with the exposure of fenpropathrin(Fen)in the region of Xinjiang.Using a previous case study as a correlational example in humans,a man who had consumed derived from Fen-poisoned fish for half a year was diagnosed with parkinsonism in China,so we speculated that the Fen may be an important risk factors for PD.In order to confirm our speculation,we performed two studies as the following:1.The neurotoxicity mechanism of Fen on the degeneration of primary neuronsTo investigate the neurotoxicity effect of Fen on primary neurons,we first isolated the primary neurons of mouse for culture in vitro.After cells were cultured for 7 days,anti-Map-2 antibody was used to label the neurons and to identify the phenotype of cultured cells.We treated the cultured neurons with a series concentration of Fen and found that Fen(100 μM)significant decreased the viability of cultured primary neurons.Subsequently,we investigated the mechanism of Fen-induced degeneration of primary neurons,and found that Fen induced the degeneration of primary neurons by disrupt the mitochondrial quality control system—mitochondrial dynamic network and mitophagy—result in oxidative stress,and the damaged mitochondrial function and synaptic transmission.2.Fenpropathrin impaired the DA system of miceTo investigate the effect of Fen on the DA nervous system,we injected Fen into the DA nervous system of mice by stereotactic injection.We found that Fen significantly impaired motor function of mice and induced degeneration of DA neurons.Subsequently,we performed a preliminary study on the mechanism on that Fen induces degeneration of DA neurons.We found that Fen induce the degeneration of DA system by disrupting the oxidation-antioxidant balance and the upregulated the expression of α-syn,disturbing the mitochondrial morphology and dynamic network,interfere with the release of neurotransmitters and autophagy.In general,we found that Fen may damage primary neurons and the DA nervous system of mice by inducing oxidative stress and disrupting the mitochondrial quality control system,and can partially mimic the pathological features of PD.We therefore suggest that long-term exposure to Fen may be an important risk factor for PD.