The C-terminal domain of the heavy chain of tetanus toxin prevents the oxidative and nitrosative stress induced by acute toxicity of 1-methyl-4-phenylpyridinium, a rat model of Parkinson's disease

The recombinant carboxyl-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) exerts neuroprotective and neurorestorative effects on the dopaminergic system of animal models of Parkinson's disease (PD). The present study aimed to determine the effect of the Hc-TeTx fragment on the markers of oxidative stress and nitrosative stress generated by the acute toxicity of 1-methyl-4-phenylpyridinium (MPP+). For this purpose, the Hc-TeTx fragment was administered once a day in three 20 mu g/kg consecutive injections into the grastrocnemius muscle of the rats, with an intra-striatal unilateral injection of 1 mu L of MPP+ [10 mu g/mL] then administered in order to cause a dopaminergic lesion. The results obtained show that the rats treated with Hc-TeTx plus MPP+ presented an increase in the expression of tyrosine hydroxylase (TH), a significantly greater decrease in the levels of the markers of oxidative stress, nitrosative stress, and neurodegeneration than that observed for the group injured with only MPP+. Moreover, it was observed that total superoxide dismutase (SOD) and copper/zinc SOD activity increased with the administration of Hc-TeTx. Finally, immunoreactivity levels were observed to decrease for the levels of 3-nitrotyrosine and the glial fibrillary acidic protein in the ipsilateral striatum of the rats treated with Hc-TeTx plus MPP+, in contrast with those lesioned with MPP+ alone. Our results demonstrate that the recombinant Hc-TeTx fragment may be a potent antioxidant and, therefore, could be suggested as a therapeutic tool against the dopaminergic neuronal impairment observed in the early stages of PD. (C) 2021 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

Automated summary

The recombinant carboxyl-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) has neuroprotective and neurorestorative effects on the dopaminergic system of animal models of Parkinson's disease. In this study, the Hc-TeTx fragment was found to decrease oxidative stress, nitrosative stress, and neurodegeneration markers induced by the acute toxicity of 1-methyl-4-phenylpyridinium. The administration of Hc-TeTx also increased the activity of superoxide dismutase and reduced the levels of 3-nitrotyrosine and glial fibrillary acidic protein.