title: 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.
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.
authors.affiliation: Laboratorio de Neurofarmacología, FCQ-Benemérita Universidad Autónoma de Puebla, Puebla, Mexico.
authors.forename: Liliana
authors.initials: L
authors.lastname: Mendieta
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bautista
authors.forename: Alejandra
authors.initials: A
authors.lastname: Sánchez
authors.forename: Jorge
authors.initials: J
authors.lastname: Guevara
authors.forename: Mireia
authors.initials: M
authors.lastname: Herrando-Grabulosa
authors.forename: José
authors.initials: J
authors.lastname: Moran
authors.forename: Rebeca
authors.initials: R
authors.lastname: Martínez
authors.forename: José
authors.initials: J
authors.lastname: Aguilera
authors.forename: Ilhuicamina Daniel
authors.initials: ID
authors.lastname: Limón
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000473:pathology; D002395:Catecholamines / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D007273:Injections, Intramuscular; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal; D009410:Nerve Degeneration / Q000139:chemically induced / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016627:Oxidopamine / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013744:Tetanus Toxin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D002395:Catecholamines; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011994:Recombinant Proteins; D013744:Tetanus Toxin; C040635:tetanus toxin fragment C; D016627:Oxidopamine; D004298:Dopamine