The role of nitric oxide on visual-evoked potentials in MPTP-induced Parkinsonism in mice

Abstract

The present study aimed to elucidate visual evoked potentials (VEP) changes in MPTP induced Parkinson’s disease (PD) and investigate the possible benefical effects of neuronal (n) and inducible (i) nitric oxide synthase (NOS) inhibitors on altered VEPs, lipid peroxidation and apoptosis. 3months old C57BL/6 mice were randomly divided into 6 groups which included control (C), 7-nitra indazole treated (7-NI), S-methylisothiourea (SMT) treated, 1,2,3,6-tetrahydropyridine (MPTP) treated, 7-NI+MPTP treated and SMT+MPTP treated. Motor activity of mice was evaluated via the pole test. At the end of the experimental period VEPs were recorded, brain and retina tissues were removed for biochemical analysis. Dopaminergic neuron death at substantia nigra (SN) was determined by immunohistochemical analysis of tyrosine hydroxylase (TH). Immunohistochemical staining was also performed to determine iNOS and nNOS in all tissue sections. Mice with experimental PD exhibited decreased motor activity. Dopaminergic cell death at pars compacta of SN (SNpc) was significantly increased in MPTP treated group compared to control. Diminished Parkinsonism symptoms were observed in 7-NI+MPTP and SMT+MPTP groups. Treatment with 7-NI and SMT decreased dopaminergic cell death in MPTP treated mice. Caspase-3 activity, nitrite/nitrate and 4-hydroxynonenal (4-HNE) levels were significantly increased in SN of MPTP treated mice compared to control. Treatment with 7-NI and SMT significantly decreased elevated caspase-3 activity, nitrite/nitrate and 4-HNE levels in SN of MPTP treated mice. No significant difference in above parameters were observed in the retina. VEP latencies were significantly prolonged in MPTP group compared to control group. 7-NI and SMT treatment caused a significant decrease in VEP latencies in MPTP treated mice compared to none treated MPTP group. This data shows that 7-NI and SMT improves prolonged VEP latencies. The protective effects of 7-NI and SMT on VEP alterations can be related to decreased dopaminergic cell death and reduced lipid peroxidation.