Neonatal chlorpyrifos exposure induces loss of dopaminergic neurons in young adult rats

Abstract

Increasing epidemiological and toxicological evidence suggests that pesticides and other environmental exposures may be associated with the development of Parkinson's disease (PD). Chlorpyrifos (CPF) is a widely used organophosphorous pesticide with developmental neurotoxicity. Its neurotoxicity, notably on the monoamine system, suggests that exposure of CPF may induce dopaminergic neuronal injury. We investigated whether neonatal exposure to CPF contributes to initiation and progression of dopaminergic neurotoxicity and explored the possible underlying mechanisms. The newborn rats were administrated 5 mg/kg CPF subcutaneously from postnatal day (PND) 11 to PND 14 daily. The effect of CPF on dopaminergic neurons, microglia, astrocyte, nuclear factor-κB (NF-κB) p. 65 and p. 38 mitogen-activated protein kinase (MAPK) signaling pathways was analyzed in the substantia nigra of rats at 12h, 24h, 72 h, 16d and 46 d after exposure. CPF-treated rats exhibited significant reduction of dopaminergic neurons at 16d and 46 d after exposure, and a significant increase in the expression of microglia and astrocytes in the substantia nigra after CPF exposure. Intense activation of NF-κB p. 65 and p. 38 MAPK inflammatory signaling pathways was observed. Our findings indicate that neonatal exposure to CPF may induce long-term dopaminergic neuronal damage in the substantia nigra mediated by the activation of inflammatory response via NF-κB p. 65 and p. 38 MAPK pathways in the nigrostriatal system.

Impact of Exposure to Fenitrothion on Vital Organs in Rats

“…Additionally, Ahmed et al [76] have previously reported similar changes of brain neurotransmitters after OPs exposure. Additionally, exposures to pesticides have been reported to cause permanent alterations in GABAergic, serotonergic [77], and dopaminergic systems [78]. …”

Environmental Exposures and Parkinson’s Disease

“…However, chronic professional and even household exposure may lead to increased PD risk [ 87 , 88 ]. In animals, neonatal exposure to the chlorpyrifos led to long-term dopaminergic cell loss and microglial activation [ 89 ]. A case-control study found that higher rates of ambient organophosphate exposure were associated with higher PD risk [ 33 ].…”

Gnetol, a Resveratrol Derivative Ameliorates Malathion-Induced Neurotoxicity through Modulating Lysosomal Membrane Permeabilization in N2a Cells

“…The morphology of cells also greatly improved after pre-supplemented with gnetol as compared with malathion treatment alone ( Figure 1B). Previously, researchers found that subcutaneous exposure of young adult rats to chlorpyrifos promotes substantial nigral dopaminergic neuronal deathmediated development of neurodegeneration, and also led to intense accumulation of microglia-and astrocyte-related neuroinflammation [19]. Similar to gnetol, pentoxifylline protects rat brains from malathioninduced oxidative stress by enhancing antioxidative enzyme levels and antioxidants, and also by functioning as an immunomodulator [20].…”