Unilateral Botulinum Neurotoxin-A Injection into the Striatum of C57BL/6 Mice Leads to a Different Motor Behavior Compared with Rats

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.

Botulinum Neurotoxin-A Injected Intrastriatally into Hemiparkinsonian Rats Improves the Initiation Time for Left and Right Forelimbs in Both Forehand and Backhand Directions

“…Three months after a second intrastriatal BoNT-A injection, IT decreased again, followed by a recurrent impairment that lasted up to a further 12 months (Figure 2A,B). Concerning the time-dependent outcome of BoNT-A application, these findings correspond to our prior results in an apomorphine-induced rotation test: injection of BoNT-A into the CPu of hemi-PD rats reduced apomorphine-induced rotation behavior significantly for at least 3 months [38,39,40,42,43,44,87]. In addition, compared with sham injections, a second BoNT-A again significantly decreased apomorphine-induced rotations, whereas the beneficial effect faded with longer post-injection survival times [58].…”

“…2 × 1 µL BoNT-A solution (Lot No. 13028A1A; List, Campbell, CA, USA; purchased via Quadratech, Surrey, UK; BoNT-A dissolved in phosphate-buffered saline (PBS) supplemented with 0.1% bovine serum albumin (BSA)) was injected with a total dose of 1 ng BoNT-A into the right CPu at two sites [ 38 , 39 , 40 , 87 ]. The respective coordinates with reference to bregma were: AP = +1.3/−0.4 mm, L = 2.6/3.6 mm to the right, and V = −5.5 mm [ 101 ].…”

Introduction to the Toxins Special Issue on Botulinum Neurotoxins in the Nervous System: Future Challenges for Novel Indications

“…For obvious reasons, primarily toxicity and toxin diffusion, these studies are still limited to animals. An example of this unusual utilization of BoNT/A is also reported by Antipova et al [ 24 ], who injected toxin directly into the striatum of mice and compared the motor behavior. The authors speculate that locally applied BoNTs could be useful for treating brain dysfunctions that require the deactivation of local brain circuitry.…”

Antidepressant-Like Properties of Intrastriatal Botulinum Neurotoxin-A Injection in a Unilateral 6-OHDA Rat Model of Parkinson’s Disease

“…In hemi-PD rats, intrastriatally applied BoNT-A has a positive effect on motor dysfunction without impairing cognitive and peripheral cholinergic functions [ 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 ].…”

“…Botulinum neurotoxin-A (BoNT-A) inhibits the release of acetylcholine (ACh) in the peripheral nervous system and is also thought to act as a local anticholinergic drug when injected intrastriatally, i.e., into the CPu in hemiparkinsonian (hemi-) PD rats. In hemi-PD rats, injection of 1 ng BoNT-A into the DA-depleted CPu significantly diminished apomorphine-induced rotational behavior for at least 3 months, the effect fading thereafter [ 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 ].…”