Research ReportIntrastriatal injection of botulinum neurotoxin-A is not cytotoxic in rat brain - A histological and stereological analysis

- In rats intrastriatal BoNT-A (1 ng) injections was performed unilaterally.
- We counted striatal cholinergic interneurons up to year after BoNT-A.
- Intrastriatal BoNT-A injection cause no loss of cholinergic interneurons.
- Cholinergic and catecholaminergic BoNT induced varicosities (BiVs) were quantified.
- BiV numbers decreases, BiV volumes increases over time after BoNT injection.

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 1 ng 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.