Botulinum neurotoxin A subtype 2 reduces pathological behaviors more effectively than subtype 1 in a rat Parkinson’s disease model

• Published in: Biochemical and biophysical research communications Vol. 447; no. 2; pp. 311 - 314
• Main Authors: Itakura, Masanori, Kohda, Tomoko, Kubo, Takeya, Semi, Yuko, Azuma, Yasu-Taka, Nakajima, Hidemitsu, Kozaki, Shunji, Takeuchi, Tadayoshi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.05.2014
• Subjects: Acetylcholine; adverse effects; Animals; Botulinum neurotoxin; botulinum toxin; Botulinum Toxins, Type A - administration & dosage; Botulinum Toxins, Type A - adverse effects; Choline O-Acetyltransferase - metabolism; Corpus Striatum - drug effects; Corpus Striatum - metabolism; disease models; Disease Models, Animal; Female; Male; memory; Oxidopamine - pharmacology; Parkinson disease; Parkinson Disease, Secondary - chemically induced; Parkinson Disease, Secondary - drug therapy; Parkinson Disease, Secondary - physiopathology; Parkinson’s disease; Proteolysis; Rats; Rotation; Subtype; Synaptosomal-Associated Protein 25 - metabolism; PBS; PD; BoNT/A; ACh; ChAT; Rats; 6-OHDA; CNS; Acetylcholine; Botulinum neurotoxin; Subtype; Parkinson’s disease
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2014.03.146

•We compared the efficacy of BoNT/A1 and BoNT/A2 in a rat Parkinson’s disease model.•BoNT/A2 more effectively reduced rotation behavior in lesioned rats than BoNT/A1.•BoNT/A2 cleavage of SNAP-25 in the striatum was more efficient than that of BoNT/A1.•Treatment with BoNT/A2 may be a clinically useful therapy for Parkinson’s disease. 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.