Abstract
Parkinson’s disease (PD) is one of the most frequent neurodegenerative disorders. Its main pathophysiological characteristic is the loss of dopaminergic neurons in the substantia nigra pars compacta followed by a lack of striatal dopaminergic input and a consequent disinhibition of tonically active cholinergic interneurons. The resulting striatal hypercholinism causes major motor symptoms in PD. Anticholinergic pharmacotherapies have antiparkinsonian effects on motor symptoms, but, due to systemic actions, also numerous severe side effects occur on a regular basis. To circumvent these side effects, a local anticholinergic therapy acting exclusively in the striatum would be reasonable. Botulinum neurotoxin-A (BoNT-A) is synthesized by Clostridium botulinum and blocks the release of acetylcholine from the presynaptic bouton. For several decades, BoNT-A has been used successfully for medical and cosmetic purposes to induce controlled paralyses of single muscles. Our group and others investigated the experimental treatment of striatal hypercholinism by the direct injection of BoNT-A into the striatum of rats and mice as well as of hemiparkinsonian animal models. This review gives an overview of the most important results of the experimental intrastriatal BoNT-A application, with a focus on hemiparkinsonian rats.
Highlights
They found that Botulinum neurotoxin-A (BoNT-A) subtype 1 and subtype 2 each suppressed methamphetamine-induced rotation behavior, but Botulinum neurotoxins (BoNTs)-A subtype 2 abolished rotation behavior in low dosages of 0.1 and 0.5 ng per CPu significantly, whereas BoNT-A subtype 1 reduced turning rate significantly only when given in a dose of 1 ng
Immunofluorescence staining for BoNT-A-cleaved SNAP-25 revealed that the effect of BoNT-A subtype 2 is limited to the injected CPu, whereas in brains injected with BoNT-A subtype 1 into the right CPu, cleaved SNAP-25 was detectable in the ipsilateral as well as in the contralateral CPu
Itakura et al concluded that BoNT-A subtype 2 should be more efficient in treatment of Parkinson’s disease (PD) symptoms than BoNT-A subtype 1, and that BoNT-A subtype 2 seemed safer for pharmacological utilization in the CPu
Summary
Parkinson’s disease (PD) is the second most frequent neurodegenerative disease. Main motor symptoms in PD are caused by axonal degeneration of dopaminergic fibers in the striatum (caudate-putamen, CPu) and subsequent or parallel loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) [1,2,3,4]. Caleo et al (2007) [44] investigated the role of neuronal activity for visual cortex maturation by temporal blockade of synaptic signal transduction For that purpose, they performed unilateral injection of BoNT-E directly into the visual cortex of rats. Injections of BoNT-A into the dorsomedial and dorsolateral striatum of CD1 mice to inhibit neurotransmitter release were studied by De Leonibus et al (2011) The role of these brain regions for learning and training orientation abilities in a plus maze test was evaluated. Due to the ability to prohibit glutamatergic signal transmission Antonucci et al (2010) tested the neuroprotective effect of BoNT-E in a rat stroke model They wanted to prevent an excessive release of cytotoxic glutamate that usually follows an ischemic event. BoNT-E injection 20 min after induction of ischemia into the hippocampus led to an enhanced survival of neurons [53]
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