Histological Features of Catecholaminergic Neuron in Substantia Nigra Induced by Paraquat Dichloride (1,1-dimethyl-4,4 bipyridinium) in Wistar Rat as A Model of Parkinson Disease

Abstract

Paraquat dichloride has been used by farmers as a herbicide to kill the grass. On the other hand, paraquat dichloride is harmful if enters to the body, causing Parkinson's disease, since it is disrupting dopamine production in the substantia nigra pars compacta or dopamine pathways Nigro striatal pathway. The study was done to fi nd out the histological changes of catecholaminergic neurons and Nigro striatal pathway caused by paraquat dichloride treatment in Wistar rats as a model of Parkinson's disease.Twenty-two Wistar rats 3,5 months old were divided into 4 groups, 5 rats each. Group I (control group) were injected with aquabidest, while groups II, III, and IV were injected intraperitoneally with paraquat dichloride in aquabidest, with the dosage 5 , 10 and 15 mg/kg bw respectively. The rats were injected once per week for 6 weeks. Three days after the last injection, the rats were anesthetized using xylasin (2 mg/kg) and ketamine (20 mg/kg) intramuscularly, and then were intracardiac perfused using physiological saline as prerinse solution, followed by 10% buffered formalin solution as a fi xative. After animals were fi xed, the brains were removed and embedded in paraffi n block and cut in 12 μm thickness for immunohistochemistry staining using tyrosine hydroxylase antibody. The results of staining then were observed under light microscope and analyzed descriptively.The results showed that the catecholaminergic neurons were distributed in the substantia nigra pars compacta in all treatment groups, however, the cell density were found decreased only in group IV. Catecholaminergic neurons appear in the bipolar and multipolar form, while dopamine 'Nigro striatal pathway' was found exist in all treatment groups. From our study, histologycally the decreased of catecholaminergic neurons is only found in rats that received paraquat dichloride in dose 15 mg/kg bw for 6 weeks.

Multifactorial theory applied to the neurotoxicity of paraquat and paraquat-induced mechanisms of developing Parkinson's disease

“…Similarly, Shimizu et al 15 found that constant exposure to low levels of PQ affected dopaminergic neurons in the nigrostriatal system of rats. More recently, Pangestiningsigh et al 16 report a decrease in the density of catecholaminergic neurons in the SNpc using histochemical preparations from rats subjected to intraperitoneal injection of PQ (15 mg/kg) over a 6-week period. 16 Laboratory investigation into animal models of PD clearly implicates PQ as a dopamine neurotoxin via chronic low-level exposure.…”

“…More recently, Pangestiningsigh et al 16 report a decrease in the density of catecholaminergic neurons in the SNpc using histochemical preparations from rats subjected to intraperitoneal injection of PQ (15 mg/kg) over a 6-week period. 16 Laboratory investigation into animal models of PD clearly implicates PQ as a dopamine neurotoxin via chronic low-level exposure. For example, intraperitoneal injection of 10 mg/kg PQ in mice injected at varied intervals for up to 3 weeks cause decreased or altered locomotor activity in conjunction with a number of physiological symptoms occurring in a dose-dependent manner, including significant decline in dopamine levels within the striatum, loss of dopaminergic neurons, degeneration of the nigrostriatal dopamine system, aggregate formation in the SNpc containing α-synuclein, and formation of LBs.…”

n-Propanol extract of boiled and fermented koro benguk (Mucuna pruriens seed) shows a neuroprotective effect in paraquat dichloride-induced Parkinson's disease rat model

“…Immunohistochemical staining using the primary antibody anti-TH to detect DA neurons has been reported by many researchers [ 17 - 19 ]. The TH-IR found in this study were similar to those reported by Nair-Roberts et al .…”

Degenerasi dan nekrosis pada neuron penyusun sistem saraf enterik di usus halus dan usus besar tikus yang diinjeksi paraquat dichloride

“…Mengecilnya ukuran neuron katekolaminergik pada kelompok perlakuan kemungkinan karena proses degenerasi. Penelitian sebelumnya menunjukkan bahwa pemberian PQ juga menyebabkan penurunan densitas neuron katekolaminergik pada substansia nigra pars kompakta tikus [22] serta terjadi penurunan jumlah neuron katekolaminergik [23]. Ada 3 macam neuron katekolaminergik yaitu neuron dopaminergik, noradrenergik dan adrenergik.…”