Hc-TeTx ameliorates LPS-induced hemiparkinsonism in rats by reducing motor asymmetry and neuroinflammation

Neuroinflammation is increasingly recognized as a central mechanism in Parkinson's disease (PD) pathogenesis, contributing to dopaminergic neurodegeneration. Current therapeutic strategies primarily manage symptoms but do not halt disease progression, especially in inflammatory contexts. The C-terminal domain of the heavy-chain of tetanus toxin (Hc-TeTx) has previously demonstrated neuroprotective effects in toxin-based PD models, suggesting a potential role in mitigating neuronal damage. However, its efficacy specifically in inflammatory-induced PD conditions, which more closely mimic certain aspects of human disease progression, remained unexplored, highlighting a critical gap in understanding its therapeutic breadth.

Researchers investigated the anti-inflammatory and neuroprotective effects of Hc-TeTx in adult male Wistar rats using a hemiparkinsonism model induced by central injection of lipopolysaccharide (LPS). Seven days post-LPS, motor coordination and gait maintenance were assessed via the elevated beam test. On day 8 post-LPS, forelimb motor asymmetry during spontaneous vertical exploration was evaluated using the cylinder test. Immediately after behavioral testing, animals were sacrificed for tissue collection. Dopaminergic degeneration was quantified by tyrosine hydroxylase (TH) immunohistochemistry in the substantia nigra pars compacta, while astroglial activation, an indicator of neuroinflammation, was assessed by glial fibrillary acidic protein (GFAP) immunohistochemistry in the striatum. The study compared Hc-TeTx-treated animals to an LPS-only control group.

LPS administration successfully induced forelimb motor asymmetry in rats, a key behavioral deficit in this PD model. Treatment with Hc-TeTx significantly attenuated this LPS-induced forelimb motor asymmetry. While specific p-values or percentages were not provided for motor asymmetry, the abstract highlights a clear beneficial effect. Hc-TeTx also tended to attenuate LPS-induced dopaminergic neurodegeneration, reflected by a reduced TH ipsilateral/contralateral ratio, though the magnitude of this reduction was not quantified. Furthermore, astroglial activation, which was markedly increased after LPS administration, also tended to be attenuated by Hc-TeTx. The beam test parameters showed no significant differences among any of the groups, suggesting Hc-TeTx's effects were specific to forelimb asymmetry and neuroinflammatory markers.

Hc-TeTx treatment significantly attenuated LPS-induced forelimb motor asymmetry, a key behavioral deficit in this inflammatory Parkinson's model.