Effectiveness of Fragment C Domain of Tetanus Toxin and Pramipexole in an Animal Model of Parkinson’s Disease
Reports indicate that striatal dopaminergic damage induced by 6-hydoxydopamine (6-OHDA) can be blocked by C-terminal domain of tetanus toxin (Hc-TeTx), suggesting possible therapeutic potential of Hc-TeTx in Parkinson’s disease (PD). Pramipexole (PPX), a D2/D3 dopaminergic agonist, is currently used in PD treatment. The purpose of this study was to gain some understanding of the actions of each drug, including potential antioxidant and anti-inflammatory effects and importantly, to determine whether the combination of the two drugs would be superior to each alone. Adult male Wistar rats were administered 6-OHDA into the dorsolateral striatum, and the effects of Hc-TeTx fragment (20 μg/kg i.m. every 24 h) for 3 days; PPX (1 mg/kg p.o., every 12 h) for 30 days and their combination on various motor and neurochemical parameters were evaluated. Behavioral tests were carried out at 15 and 30 days post-treatments. At day 31, the animals were sacrificed and the levels of tyrosine hydroxylase (TH), reflecting dopaminergic activity in both striatum and substantia nigra, were evaluated. In addition, indices of astrogliosis, microgliosis, as well as oxidative stress in the striatum were determined. Both Hc-TeTx and PPX ameliorated the motor and neurochemical deficits induced by 6-OHDA lesion; however, the combination of the two drugs was not superior to each alone. Hence, at concentrations used in this study, no significant advantage in combining Hc-TeTx with PPX was noted. Although the results suggest similar neurochemical effects of the two compounds, further evaluation of different concentrations of Hc-TeTx and PPX as potential intervention in PD is warranted.
KeywordsTetanus toxin 6-Hydroxydopamine Astrogliosis Microgliosis Oxidative stress Superoxide dismutase Parkinson’s disease
Glial fibrillary acidic protein
C-terminal domain of heavy-chain tetanus toxin
Ioninized calcium binding adaptor molecule 1
Substantia nigra pars compacta
Reactive oxygen species
We thank Ana Candalija for her help in synthesizing Hc-TeTx fragment and Aldredo López from INNN-MVS for his technical assistance.
This work was supported by grants from PRODEP-SEP (N-PTC-472) and by VIEP-BUAP (2016-2017); F. Patricio was supported by a scholarship from CONACYT-Mexico (581481).
Compliance with Ethical Standards
All animal procedures were carried out in accordance with the Mexican Council for Care and Use of Laboratory Animals and the Norma Oficial Mexicana NOM-062-ZOO-1999
Conflict of Interest
The authors declare that they have no conflicts of interest.
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