Botulinum neurotoxin A subtype 2 reduces pathological behaviors more effectively than subtype 1 in a rat Parkinson's disease model.
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.
Laboratory of Veterinary Pharmacology, Graduate School of Life and Environmental Science, Osaka Prefecture University, 1-58 Rinku Ourai Kita, Izumisano-shi, Osaka 5988531, Japan.
Masanori
M
Itakura
Laboratory of Veterinary Epidemiology, Graduate School of Life and Environmental Science, Osaka Prefecture University, 1-58 Rinku Ourai Kita, Izumisano-shi, Osaka 5988531, Japan.
Tomoko
T
Kohda
Laboratory of Veterinary Pharmacology, Graduate School of Life and Environmental Science, Osaka Prefecture University, 1-58 Rinku Ourai Kita, Izumisano-shi, Osaka 5988531, Japan.
Takeya
T
Kubo
Laboratory of Veterinary Pharmacology, Graduate School of Life and Environmental Science, Osaka Prefecture University, 1-58 Rinku Ourai Kita, Izumisano-shi, Osaka 5988531, Japan.
Yuko
Y
Semi
Laboratory of Veterinary Pharmacology, Graduate School of Life and Environmental Science, Osaka Prefecture University, 1-58 Rinku Ourai Kita, Izumisano-shi, Osaka 5988531, Japan.
Yasu-Taka
YT
Azuma
Laboratory of Veterinary Pharmacology, Graduate School of Life and Environmental Science, Osaka Prefecture University, 1-58 Rinku Ourai Kita, Izumisano-shi, Osaka 5988531, Japan. Electronic address: hnakajima@vet.osakafu-u.ac.jp.
Hidemitsu
H
Nakajima
Laboratory of Veterinary Epidemiology, Graduate School of Life and Environmental Science, Osaka Prefecture University, 1-58 Rinku Ourai Kita, Izumisano-shi, Osaka 5988531, Japan.
Shunji
S
Kozaki
Laboratory of Veterinary Pharmacology, Graduate School of Life and Environmental Science, Osaka Prefecture University, 1-58 Rinku Ourai Kita, Izumisano-shi, Osaka 5988531, Japan.
Tadayoshi
T
Takeuchi
D000818:Animals; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage* / Q000009:adverse effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D059748:Proteolysis; D051381:Rats; D012399:Rotation; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism
D050825:Synaptosomal-Associated Protein 25; D016627:Oxidopamine; D002795:Choline O-Acetyltransferase; D019274:Botulinum Toxins, Type A
Acetylcholine; Botulinum neurotoxin; Parkinson’s disease; Rats; Subtype