Behavioral and structural effects of unilateral intrastriatal injections of botulinum neurotoxin a in the rat model of Parkinson's disease

Abstract

Botulinum neurotoxin (BoNT) inhibits the release of acetylcholine from presynaptic vesicles through its proteinase activity cleaving the SNARE complex. Parkinson's disease (PD) is associated with locally increased cholinergic activity in the striatum. Therefore, the present study investigates the effect of unilateral intrastriatal BoNT-A injection in naïve rats on striatal morphology; i.e., the total number of Nissl-stained neurons and the volume of caudate-putamen (CPu) were estimated. Furthermore, stainings for markers of gliosis (glial fibrillary acidic protein) and microglia (Iba1) were performed. In addition, the potential beneficial effects of a unilateral intrastriatal injection of BoNT-A on motor activity in the rat model of hemi-PD were evaluated. Hemi-PD was induced by unilateral injection of 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle. Six weeks later, rats received an ipsilateral intrastriatal injection of BoNT-A. Behaviorally, motor performance was tested. The total number of CPu neurons and the striatal volume were not significantly different between the BoNT-A-injected right and the intact left hemispheres of naïve rats. In hemi-PD rats, intrastriatal BoNT-A abolished apomorphine-induced rotations, increased amphetamine-induced rotations, and tended to improve left forelimb usage. Forced motor function in the accelerod test was not significantly changed by BoNT-A, and open field activity was also unaltered compared with sham treatment. Thus, intrastriatal BoNT-A affects spontaneous motor activity of hemi-PD rats to a minor degree compared with drug-induced motor function. In the future, tests assessing the cognitive and emotional performance should be performed to ascertain finally the potential therapeutic usefulness of intrastriatal BoNT-A for PD.