C-terminal Domain of the Heavy Chain of Tetanus Toxin Ameliorate Lipopolysaccharide Induced Hemiparkinsonism in Rats

Neuroinflammation is recognized as a central mechanism in Parkinson's disease (PD) pathogenesis. The C-terminal domain of the heavy-chain of tetanus toxin (Hc-TeTx) has shown neuroprotective effects in toxin-based PD models, but its efficacy in inflammatory-induced PD conditions remain unexplored. To test this possibility, we used the hemiparkinsonism model induced by central injection of lipopolysaccharide (LPS) to evaluate potential antiinflammatory effects of Hc-TeTx in adult male Wistar rats. Seven days post LPS-injection motor coordination and gait maintenance were assessed using elevated beam test. The day after, that is 8 days post LPS-injection, the cylinder test was used to assess forelimb motor asymmetry during spontaneous vertical exploration. Immediately after this test the animals were sacrificed for tissue collection. Dopaminergic degeneration was assessed by immunohistochemical quantification of tyrosine hydroxylase in substantia nigra pars compacta. Astroglial activation, reflective of neuroinflammation was evaluated by glial fibrillary acidic protein in the striatum. LPS administration caused forelimb motor asymmetry, which was significantly attenuated by Hc-TeTx treatment. Hc-TeTx also tended to attenuate LPS-induced dopaminergic neurodegeneration reflected by a reduced TH ipsilateral/contralateral ratio, as well as astroglial activation that was markedly increased after LPS administration. Beam test parameters showed no significant differences among groups. Although further verification and mechanistic studies are needed, current results support potential utility of Hc-TeTx in an inflammatory model of PD.