The effect of İNOS AND NNOS on visual evoked potentials in experimental parkinson's disease

The main pathology in Parkinson's Disease (PD) is degeneration of the nigrostriatal dopaminergic system and the reduction of dopamine in the basal ganglia. The selective loss of dopaminergic neurons at pars compacta of substantia nigra (SNpc) leads to PD. Visual evoked potentials (VEPs) have been shown to be a sensetive marker in visual system changes of PD. The exact mechanism of these changes are unknown. Nitric oxide (NO) plays an important role in experimental PD. Increased activity of neuronal (n) and inducible (i) nitric oxide synthase (NOS) play a role in elevated nitric oxide synthesis. The present study aimed to elucidate VEP changes in MPTP induced PD and investigate the possible benefical effects of nNOS and iNOS inhibitors on altered VEPs, lipid peroxidation and apoptosis occuring in experimental mice model of the disease.3 months 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, SMT+MPTP treated. The MPTP toxin was applied twice daily with 12 hours intervals for two days with a total given dose of 4x20 mg/kg. The nNOS inhibitor, 7-NI, was dissolved in peanut oil and given at a dose of 50 mg/kg, 1 hour before MPTP administration. The iNOS inhibitor, SMT, was dissolved in physiological saline and administrated i.p. at a dose of 10 mg/kg, 15 minutes before MPTP administration.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 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 in 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 of experimental groups.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 in MPTP group. The protective effects of 7-NI and SMT on VEP alterations can be related to decreased dopaminergic cell death and reduced lipid peroxidation.