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

Brain Res. 2016 Jan 1:1630:18-24. doi: 10.1016/j.brainres.2015.10.056. Epub 2015 Nov 10.

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.

Keywords: Basal ganglia; Botulinum neurotoxin A; Rat brain; Striatum; Unbiased stereology.

MeSH terms

  • Animals
  • Botulinum Toxins, Type A / administration & dosage*
  • Botulinum Toxins, Type A / adverse effects
  • Cell Count
  • Cell Size
  • Central Nervous System Agents / administration & dosage*
  • Central Nervous System Agents / adverse effects
  • Choline O-Acetyltransferase / metabolism
  • Drug Evaluation, Preclinical
  • Immunohistochemistry
  • Interneurons / cytology*
  • Interneurons / drug effects*
  • Male
  • Neostriatum / cytology*
  • Neostriatum / drug effects*
  • Rats, Wistar
  • Time
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Central Nervous System Agents
  • Tyrosine 3-Monooxygenase
  • Choline O-Acetyltransferase
  • Botulinum Toxins, Type A