Striatal transplantation in a rodent model of multiple system atrophy: Effects on L‐Dopa response

Abstract

Progressive degeneration of striatal projection neurons is thought to account for the loss of L-Dopa response observed in the majority of patients with the parkinsonian variant of multiple system atrophy (MSA-P). Here we have investigated the effects of E14 embryonic striatal allografts on dopaminergic responsiveness in the unilateral double-lesion rat model of MSA-P by using tests of complex motor behavior. Both sham and graft animals showed an increase in apomorphine-induced rotations as well as an improvement in cylinder test performance following surgical intervention. In contrast, L-Dopa responsiveness of stepping behavior was improved only in grafted animals. The restoration of apomorphine-induced rotation correlated with the P-zone volume of grafts. Our findings indicate that transplantation of embryonic striatal grafts might, at least to some extent, restore responsiveness to L-Dopa in tasks of complex motor behavior. Therefore, striatal transplantation should be further defined preclinically as a possible therapeutic option for patients with MSA-P and a failing L-Dopa response.

Evaluation of a multiple system atrophy model in rats using multitracer microPET

“…Using a Hamilton syringe (33-gauge) fitted with an automated microsyringe pump (Harvard Apparatus, Holiston, MA), the five rats were unilaterally injected with 8 μg 6-OHDA (Sigma, St. Louis, MO) in 4 μl amounts of 0.9% saline with 0.1% ascorbic acid, at a rate of 1 μl/min, into the right medial forebrain bundle (MFB) at coordinates AP −2.2 mm, L +1.5 mm, and V −8.0 mm, with the tooth bar set at +4.5 mm [11]. After injection, the needle was maintained in place for 3 min to prevent toxin leakage and next withdrawn over 5 min.…”

“…Although apomorphine-induced rotation tests have been performed to determine whether MSA-p has been generated in such animals, the number of drug-induced rotations has been found to depend on the timing of testing after injection [4,11,16]. In contrast, novel neuroimaging methods may be useful to clarify whether the rodent model adequately mimics human neurodegenerative diseases [5].…”

Recent developments in multiple system atrophy

“…Research in the double toxin-double lesion rat model has evidenced the possibility of ''turning MSA into PD'' phenotype and recovering dopaminergic responsiveness by striatal allografting [85,173,201]. Current studies target the role of GCI-pathology on graft survival and functional activity [176].…”

A Novel Animal Model of Parkinson’s Disease Using Optogenetics: Representation of Various Disease Stages by Modulating the Illumination Parameter

“…Five rats received unilateral injections of 8 µg of 6-OHDA (Sigma, St. Louis, MO, USA) in 4 µL of 0.9% saline with 0.1% ascorbic acid into the right MFB at the following coordinates: AP −2.2 mm, L +1.5 mm relative to the bregma, and V −8.0 mm from the dura, with the tooth bar set at +4.5 mm [30]. Six rats received unilateral injections of 7 µg of 6-OHDA in 3 µL of 0.9% saline with 0.1% ascorbic acid into the right striatum at the following coordinates: AP +1.2/+0.2 mm, L +2.5/3.0 mm, and V −5.0 mm from the dura [31].…”