TY - JOUR
T1 - 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
AU - Mendieta, Liliana
AU - Bautista, Elizabeth
AU - Sánchez, Alejandra
AU - Guevara, Jorge
AU - Herrando-Grabulosa, Mireia
AU - Moran, José
AU - Martínez, Rebeca
AU - Aguilera, José
AU - Limón, Ilhuicamina Daniel
PY - 2012/10/1
Y1 - 2012/10/1
N2 - 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. © 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society.
AB - 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. © 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society.
KW - 6-Hydroxydopamine, Motor asymmetry
KW - C-terminal domain of tetanus toxin
KW - Cylinder test
KW - Dopamine
KW - Neuroprotection
KW - Parkinson's disease
KW - Stepping test
U2 - https://doi.org/10.1016/j.neures.2012.08.006
DO - https://doi.org/10.1016/j.neures.2012.08.006
M3 - Article
VL - 74
SP - 156
EP - 167
JO - Neuroscience Research
JF - Neuroscience Research
SN - 0168-0102
ER -