gms | German Medical Science

Objective: A rat model of Parkinson’s disease (PD) is based on unilateral injections of 6-OHDA into the medial forebrain bundle (MFB) of the rat, resulting in a complete loss of nigral dopamin­ergic neurons and leading to a depletion of dopamine (DA) within the striatum inducing motor deficits. The Staircase test (Montoya et al., 1991) was established to measure side-specific deficits in skilled paw reaching in rats. The aim of this study is to investigate the sensitivity of the test to detect functional recovery of grafted PD rats based on the number of pellets placed on each step.

Methods: 53 rats were pre-trained for 22 days in the staircase boxes. 10 animals were allocated to the control group, and 43 were lesioned in the right MFB with 6-OHDA. After a month, half of the lesioned animals received a striatal graft of cells derived from rat E14 ventral mes­en­cepha­lon. Drug-induced rotation tests were carried out at 4 weeks post-lesion and post-graft. The groups were then allotted to one of the following conditions: HIGH (6 stairwells baited with 10 pellets each), or LOW (6 stairwells baited with 2 pellets each). Free-choice test (bilateral) was performed 5 weeks after the transplantation for 25 consecutive days, followed by 14 days of forced-choice test (only baiting the left side). Two weeks after, the groups were crossed over by switching the conditions. Survival and integration of grafted neurons were assessed by immunohistochemical analysis.

Results: Drug-induced rotation testing after lesion showed a significant lesion effect (p<0.001). Four weeks after grafting the transplanted groups showed a significant compensation, indicating good graft survival, and graft dopamine release within the striatum. At pre-training, the rats retrieved almost all the pellets bilaterally. After transplantation there was a significant graft effect in the HIGH condition group in terms of pellets taken (p<0.001) in the free-choice and in the forced-choice test. This was not observed in the LOW condition group in any of the variants analyzed (pellets taken, eaten, and success rate).

Conclusions: Our results affirm that the transplant of DAergic cells into the dopamine depleted striatum is able to partially restore skilled forelimb motor deficits evaluated by the paw reaching test in a PD model in the rat. Furthermore, we observed that the density of pellets on each step plays a role in the outcome with only the HIGH condition showing a significant recovery of the number of pellets taken in the paw-reaching test.