title: Intrastriatal injection of botulinum neurotoxin-A is not cytotoxic in rat brain - A histological and stereological analysis.
abstract: Parkinson's disease (PD) is caused by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, resulting in a deficiency of dopamine in the striatum and an increased release of acetylcholine by tonically active interneurons. Botulinum neurotoxin-A (BoNT-A) is well known for blocking transmitter release by cholinergic presynaptic terminals. Treating striatal hypercholinism by local application of BoNT-A could be a possible new local therapy option of PD. In previous studies of our group, we analyzed the effect of BoNT-A injection into the CPu of 6-OHDA lesioned hemiparkinsonian rats. Our studies showed that BoNT-A application in hemiparkinson rat model is capable of abolishing apomorphine induced rotations for approximately 3 months. Regularly occurring axonal swellings in the BoNT-A infiltrated striata were also discovered, which we named BoNT-A induced varicosities (BiVs). Résumé: Here we investigated the long-term effect of the injection of 1ng BoNT-A into the right CPu of naive Wistar rats on the number of ChAT-ir interneurons as well as on the numeric density and the volumetric size of the BiVs in the CPu. Significant differences in the number of ChAT-ir neurons between the right BoNT-A treated CPu and the left untreated CPu were not detected up to 12 month post BoNT-A injection. The numeric density of BiVs in the treated CPu reached a maximum 3 months after BoNT-A treatment and decreased afterwards, whereas the volume of single BiVs increased steadily throughout the whole time course of the experiment.
authors.affiliation: Department of Anatomy, Rostock University Medical Center, Gertrudenstraße 9, 18057 Rostock, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Mehlan
authors.affiliation: Department of Anatomy, Rostock University Medical Center, Gertrudenstraße 9, 18057 Rostock, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Brosig
authors.affiliation: Department of Anatomy, Rostock University Medical Center, Gertrudenstraße 9, 18057 Rostock, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Schmitt
authors.affiliation: Department of Neurology, Rostock University Medical Center, Gehlsheimer Straße 20, 18147 Rostock, Germany.
authors.forename: Eilhard
authors.initials: E
authors.lastname: Mix
authors.affiliation: Department of Anatomy, Rostock University Medical Center, Gertrudenstraße 9, 18057 Rostock, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wree
authors.affiliation: Department of Anatomy, Rostock University Medical Center, Gertrudenstraße 9, 18057 Rostock, Germany. Electronic address: alexander.hawlitschka@uni-rostock.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hawlitschka
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage* / Q000009:adverse effects; D002452:Cell Count; D048429:Cell Size; D002491:Central Nervous System Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D007150:Immunohistochemistry; D007395:Interneurons / Q000166:cytology* / Q000187:drug effects*; D008297:Male; D017072:Neostriatum / Q000166:cytology* / Q000187:drug effects*; D017208:Rats, Wistar; D013995:Time; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D002491:Central Nervous System Agents; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; D019274:Botulinum Toxins, Type A
keywords: Basal ganglia; Botulinum neurotoxin A; Rat brain; Striatum; Unbiased stereology