The C-terminal domain of the heavy chain of tetanus toxin given by intramuscular injection causes neuroprotection and improves the motor behavior in rats treated with 6-hydroxydopamine

• Published in: Neuroscience research Vol. 74; no. 2; pp. 156 - 167
• Main Authors: Mendieta, Liliana, Bautista, Elizabeth, Sánchez, Alejandra, Guevara, Jorge, Herrando-Grabulosa, Mireia, Moran, José, Martínez, Rebeca, Aguilera, José, Limón, Ilhuicamina Daniel
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.10.2012
• Subjects: 6-Hydroxydopamine, Motor asymmetry; Animals; Apoptosis - drug effects; Astrocytes - pathology; C-terminal domain of tetanus toxin; Catecholamines - metabolism; Chromatography, High Pressure Liquid; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Corpus Striatum - pathology; Cylinder test; Dopamine; Dopamine - metabolism; Drug Evaluation, Preclinical; Injections, Intramuscular; Locomotion - drug effects; Locomotion - physiology; Male; Motor Activity - drug effects; Motor Activity - physiology; Muscle, Skeletal; Nerve Degeneration - chemically induced; Nerve Degeneration - prevention & control; Neuroprotection; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Oxidopamine - toxicity; Parkinson's disease; Parkinsonian Disorders - chemically induced; Parkinsonian Disorders - drug therapy; Peptide Fragments - administration & dosage; Peptide Fragments - pharmacology; Peptide Fragments - therapeutic use; Protein Structure, Tertiary; Rats; Rats, Wistar; Recombinant Proteins - administration & dosage; Recombinant Proteins - pharmacology; Recombinant Proteins - therapeutic use; Stepping test; Tetanus Toxin - administration & dosage; Tetanus Toxin - pharmacology; Tetanus Toxin - therapeutic use; Neuroprotection; Parkinson's disease; Dopamine; C-terminal domain of tetanus toxin; 6-Hydroxydopamine, Motor asymmetry; Cylinder test; Stepping test
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2012.08.006

[Display omitted] ► The intramuscular injection of Hc-TeTx improves motor behavior in hemiparkinsonism rats. ► The pretreatment with Hc-TeTx in rats prevents the neurodegeneration caused by the 6-OHDA. ► The Hc-TeTx could be a potential therapeutic agent in pathologies such as Parkinson's disease. We have previously shown that the intrastriatal injection of the C-terminal domain of tetanus toxin (Hc-TeTx) protects the nigrostriatal-dopaminergic pathways and improves motor behavior in hemiparkinsonism-rat models caused by MPP+ (1-methyl-4-phenylpyridinium). Here we have investigated the protective effects of the intramuscular application of the Hc-TeTx on motor asymmetry and neurodegeneration in the striatum of 6-hydroxydopamine (6-OHDA)-treated rats. Adult male rats were intramuscularly injected with the recombinant Hc-TeTx protein (0.1–20μg/kg, daily) 3days before the stereotaxic injection of 6-OHDA into the left striatum. Our results showed that the motor-improvement functions were extended for 4weeks in all Hc-TeTx-treated groups, obtaining the maximum performance with the highest dose of Hc-TeTx (20μg/kg). The improvements found were 97%, 87%, and 70% in the turning behavior, stepping test, and cylinder test, respectively. The striatal levels of dopamine and its metabolites did not vary compared to the control group. Moreover, the peripheral treatment with Hc-TeTx in rats prevents, for 30days, the neurodegeneration in the striatum caused by the toxicity of the 6-OHDA. Our results lead us to believe that the Hc-TeTx could be a potential therapeutic agent in pathologies caused by impairment of dopaminergic innervations such as Parkinson's disease.