Abstract
Different morphological changes in the caudate-putamen (CPu) of naïve rats and mice were observed after intrastriatal botulinum neurotoxin-A (BoNT-A) injection. For this purpose we here studied various motor behaviors in mice (n = 46) longitudinally up to 9 months after intrastriatal BoNT-A administration as previously reported for rats, and compared both outcomes. Apomorphine- and amphetamine-induced rotational behavior, spontaneous motor behavior, as well as lateralized neglect were studied in mice after the injection of single doses of BoNT-A into the right CPu, comparing them with sham-injected animals. Unilateral intrastriatal injection of BoNT-A in mice induced significantly increased contralateral apomorphine-induced rotations for 1 to 3 months, as well as significantly increased contralateral amphetamine-induced rotations 1 to 9 months after injection. In rats (n = 28), unilateral BoNT-A injection also induced significantly increased contralateral apomorphine-induced rotations 3 months after injection, but did not provoke amphetamine-induced rotations at all. Lateralized sensorimotor integration, forelimb preference, and forelimb stepping were significantly impaired on the left side. The differences in motor behaviors between rats and mice may be caused by different BoNT-A effects on cholinergic and catecholaminergic fibers in rat and mouse striata, interspecies differences in striatal receptor densities, and different connectomes of the basal ganglia.
Highlights
Parkinson’s disease (PD) is a common chronic progressive age-related neurodegenerative movement disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta and, subsequently, of dopamine in the caudate-putamen (CPu) [1,2,3]
botulinum neurotoxin-A (BoNT-A) unilaterally injected into the CPu in naïve mice differentially affected various motor behaviors
Unilateral intrastriatal BoNT-A induced significant contralateral amphetamine-induced rotations from 1 to 9 months post injection, which is completely opposite to the reaction found in rats
Summary
Parkinson’s disease (PD) is a common chronic progressive age-related neurodegenerative movement disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta and, subsequently, of dopamine in the caudate-putamen (CPu) [1,2,3]. Dopamine deficit causes a profound impairment of neuronal circuits in the basal ganglia [4,5,6,7], and an increased release of acetylcholine by tonically active striatal interneurons [8,9,10,11,12]. In order to circumvent general anticholinergic drug effects, we tested a local intrastriatal injection of botulinum neurotoxin-A (BoNT-A) [16,17,18,19,20]. In the experimental 6-OHDA-induced hemiparkinsonian (hemi-PD) rat model, intrastriatal application of BoNT-A abolished apomorphine-induced rotational behavior—most probably by blocking acetylcholine, the release of cholinergic terminals, and/or inducing changes in receptor densities [16,17,18,19,20,21,22,23]. The unilateral intrastriatal BoNT-A injection induced rotational behavior in naïve rats without 6-OHDA-induced hemi-PD. Following the injection of 1 ng BoNT-A into the right CPu, rats showed 2–4 apomorphine-induced rotations per min in the direction of the injection site for two months, and rotated tentatively to the contralateral side thereafter [19]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
