Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hawlitschka, A; Holzmann, C; Witt, S; Spiewok, J; Neumann, AM; Schmitt, O; Wree, A; Antipova, V.
Intrastriatally injected botulinum neurotoxin-A differently effects cholinergic and dopaminergic fibers in C57BL/6 mice.
Brain Res. 2017; 1676(6):46-56
Doi: 10.1016/j.brainres.2017.09.016
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Antipova Veronica Alexandra
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- Abstract:
- Unilateral intrastriatal BoNT-A injection abolished apomorphine-induced rotational behavior in a rat model of hemiparkinsonism (hemi-PD) up to 6months. It was hypothesized that the beneficial effect of botulinum neurotoxin-A (BoNT-A) grounded on the reduction of the Parkinson's diseases (PD) associated striatal hypercholinism. Intrastriatal injection of BoNT-A was not cytotoxic in rat brain, but neuronal fiber swellings in the BoNT-A infiltrated striata appeared and named BoNT-A-induced varicosities (BiVs). In the rat BiVs were immunoreactive (ir) either for choline acetyltransferase (ChAT) or tyrosine hydroxylase (TH). In the present study the structural effect of unilateral intrastriatal BoNT-A injection in the naïve mouse brain was analyzed to extend possible therapeutic BoNT-A applications to genetical Parkinsonian strains. We investigated the effect of a single dose of 25pg BoNT-A injected into the right caudate-putamen (CPu) for up to 9months, and of increasing doses up to 200pg on striatal volume, number of ChAT-ir interneurons, and numeric density and volume of the ChAT-ir BiVs in comparison to the uninjected hemisphere. Intrastriatal BoNT-A injection did not alter the number of ChAT-ir interneurons irrespective of survival time and dosage tested. However, the numeric density of the ChAT-ir BiVs at a dose of 25pg increased from 1 to 3months after BoNT-A, followed by a time dependent decrease. In parallel, with increasing BoNT-A survival time, the mean BiV volume increased as the number of small BiVs decreased. Interestingly, in contrast to rats we did not find TH-ir BiVs in BoNT-A injected mouse striatum. Copyright © 2017 Elsevier B.V. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Botulinum Toxins, Type A - toxicity
- Caudate Nucleus - drug effects
- Caudate Nucleus - metabolism
- Caudate Nucleus - pathology
- Cell Count -
- Cell Size - drug effects
- Cell Survival - drug effects
- Cholinergic Neurons - drug effects
- Cholinergic Neurons - metabolism
- Cholinergic Neurons - pathology
- Disease Models, Animal -
- Dopaminergic Neurons - drug effects
- Dopaminergic Neurons - metabolism
- Dopaminergic Neurons - pathology
- Dose-Response Relationship, Drug -
- Interneurons - drug effects
- Interneurons - metabolism
- Interneurons - pathology
- Male -
- Mice, Inbred C57BL -
- Organ Size -
- Parkinsonian Disorders - metabolism
- Parkinsonian Disorders - pathology
- Putamen - drug effects
- Putamen - metabolism
- Putamen - pathology
- Time Factors -
- Find related publications in this database (Keywords)
- Botulinum neurotoxin-A
- Striatum
- Basal ganglia
- Mouse brain
- Unbiased stereology
- Interneuron