Repeated intrastriatal application of botulinum neurotoxin-A did not influence choline acetyltransferase-immunoreactive interneurons in hemiparkinsonian rat brain - A histological, stereological and correlational analysis.

Abstract

In Parkinson's disease, dopamine depletion leads to hyperactivity of cholinergic interneurons in the caudate-putamen (CPu). Botulinum neurotoxin-A (BoNT-A) inhibits the release of acetylcholine in the peripheral nervous system and is also thought to act as a local anticholinergic drug when injected intrastriatally. In hemiparkinsonian (hemi-PD) rats, a unilateral intrastriatal injection of 1 ng BoNT-A significantly diminished apomorphine-induced rotation behavior for at least 3 months, the effect fading thereafter. A second intrastriatal BoNT-A application, 6 months after the first one, led to a stronger and longer-lasting, beneficial behavioral reaction. As a single BoNT-A injection was not cytotoxic in the rat striatum and resembled BoNT-A treatment in clinical practice, here, we investigated the structural outcome of repeated intrastriatal BoNT-A injections with respect to striatal volume, the number of choline acetyltransferase-immunoreactive (ChAT-ir) interneurons and of the length of their dendritic arbors, and the numeric density of ChAT-ir BoNT-A-induced varicosities (BiVs). Repeated unilateral intrastriatal BoNT-A application decreased the volume of the injected CPu, but did not significantly change the number of striatal ChAT-ir interneurons. Also, the total dendrite length of ChAT-ir interneurons after repeated BoNT-A application resembled the values in double vehicle-injected hemi-PD rats. In repeatedly BoNT-A-injected hemi-PD rats, the numeric density of ChAT-ir BiVs in the CPu was increased compared with rats only intrastriatally injected once with BoNT-A. Even repeated BoNT-A injections in rat striata did not cause substantial morphological changes in ChAT-ir neuron, except for the increased numeric density of ChAT-ir BiVs.

• Authors: Alexander Hawlitschka, Charlotte Berg, Oliver Schmitt, Carsten Holzmann, Andreas Wree, Veronica Antipova
• Journal: Brain research (Brain Res) Vol. 1742 Pg. 146877 (09 01 2020) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 32387181 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Choline O-Acetyltransferase
• Botulinum Toxins
• Botulinum Toxins, Type A

Topics

• Animals
• Behavior, Animal (drug effects)
• Botulinum Toxins (administration & dosage, pharmacology)
• Botulinum Toxins, Type A (administration & dosage, metabolism, pharmacology)
• Brain (drug effects, pathology)
• Choline O-Acetyltransferase (metabolism)
• Corpus Striatum (drug effects)
• Disease Models, Animal
• Interneurons (drug effects, metabolism)
• Male
• Motor Activity (drug effects)
• Neostriatum (drug effects)
• Parkinson Disease (drug therapy, physiopathology)
• Parkinsonian Disorders (drug therapy, physiopathology)
• Rats
• Rats, Wistar