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Botulinum neurotoxin A subtype 2 reduces pathological behaviors more effectively than subtype 1 in a rat Parkinson’s disease model
Authors:Masanori Itakura  Tomoko Kohda  Takeya Kubo  Yuko Semi  Yasu-Taka Azuma  Hidemitsu Nakajima  Shunji Kozaki  Tadayoshi Takeuchi
Affiliation:1. Laboratory of Veterinary Pharmacology, Graduate School of Life and Environmental Science, Osaka Prefecture University, 1-58 Rinku Ourai Kita, Izumisano-shi, Osaka 5988531, Japan;2. Laboratory of Veterinary Epidemiology, Graduate School of Life and Environmental Science, Osaka Prefecture University, 1-58 Rinku Ourai Kita, Izumisano-shi, Osaka 5988531, Japan
Abstract:Recent reports indicate that interruption of acetylcholine release by intrastriatal injection of botulinum neurotoxin type A (BoNT/A) in a rat Parkinson’s disease model reduces pathogenic behavior without adverse side effects such as memory dysfunction. Current knowledge suggests that BoNT/A subtype 1 (BoNT/A1) and BoNT/A subtype 2 (BoNT/A2) exert different effects. In the present study, we compared the effects of BoNT/A1 and BoNT/A2 on rotation behavior and in vivo cleavage of presynaptic protein SNAP-25 in a rat unilateral 6-hydroxydopamine-induced Parkinson’s disease model. BoNT/A2 more effectively reduced pathogenic behavior by efficiently cleaving SNAP-25 in the striatum compared with that of BoNT/A1. Our results suggest that BoNT/A2 has greater clinical therapeutic value for treating subjects with Parkinson’s disease compared to that of BoNT/A1.
Keywords:6-OHDA, 6-hydroxydopamine   ACh, acetylcholine   BoNT/A, botulinum neurotoxin subtype A   CNS, central nervous system   ChAT, choline acetyltransferase   PD, Parkinson&rsquo  s disease   PBS, phosphate-buffered saline
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