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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.
- Source :
-
Neuroscience research [Neurosci Res] 2012 Oct; Vol. 74 (2), pp. 156-67. Date of Electronic Publication: 2012 Sep 01. - Publication Year :
- 2012
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Abstract
- 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.<br /> (Copyright © 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)
- Subjects :
- Animals
Apoptosis drug effects
Astrocytes pathology
Catecholamines metabolism
Chromatography, High Pressure Liquid
Corpus Striatum drug effects
Corpus Striatum pathology
Dopamine metabolism
Drug Evaluation, Preclinical
Injections, Intramuscular
Locomotion drug effects
Locomotion physiology
Male
Motor Activity physiology
Muscle, Skeletal
Nerve Degeneration chemically induced
Nerve Degeneration prevention & control
Neuroprotective Agents administration & dosage
Neuroprotective Agents pharmacology
Parkinsonian Disorders chemically induced
Peptide Fragments administration & dosage
Peptide Fragments pharmacology
Protein Structure, Tertiary
Rats
Rats, Wistar
Recombinant Proteins administration & dosage
Recombinant Proteins pharmacology
Recombinant Proteins therapeutic use
Tetanus Toxin administration & dosage
Tetanus Toxin pharmacology
Corpus Striatum metabolism
Motor Activity drug effects
Neuroprotective Agents therapeutic use
Oxidopamine toxicity
Parkinsonian Disorders drug therapy
Peptide Fragments therapeutic use
Tetanus Toxin therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1872-8111
- Volume :
- 74
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Neuroscience research
- Publication Type :
- Academic Journal
- Accession number :
- 22967672
- Full Text :
- https://doi.org/10.1016/j.neures.2012.08.006