PMC

Dopamine- and adenosine 3,5-monophosphate regulated phosphoprotein (DARPP32) immunohistochemistry was used to visualize the striatal projection neurons. Three sections in the rostral, middle and caudal section of the striatum are shown per group.

All 54 male Wistar rats underwent 6-hydroxydopamine (6-OHDA) lesion surgery. The first behavioural assessment included amphetamine induced rotation, cylinder and stepping test with saline (S1) or L-dopa (LD1) treatment. Animals were then randomized into the three experimental groups according to rotation behaviour and L-dopa response. Groups 1 and 2 received the additional quinolinic acid (QA) lesions: group 1: 6-OHDA+severe QA and group 2: 6-OHDA+mild QA, while group 3 served as the Parkinson´s disease control group with the 6-OHDA lesion only. Afterwards, the second behavioural assessment including cylinder and stepping test with saline (S2) or L-dopa treatment (LD2), amphetamine and apomorphine induced rotation was performed. Finally, animals were sacrificed for histological purposes.

L-dopa response patterns (A-F) and related histology (G-H). Data are illustrated as mean ± standard error. L-dopa responsiveness was evaluated by cylinder and stepping test. All animals received the initial 6-hydroxydopamine (6-OHDA) lesion prior to the first behavioural assessment, while only groups 1 and 2 received the additional quinolinic acid (QA) lesions before the second behavioural assessment: group 1: 6-OHDA+severe QA; group 2: 6-OHDA+mild QA; group 3: 6-OHDA. At the first behavioural assessment (A,C,E), all experimental groups showed a significant motor improvement after L-dopa administration compared to saline treatment in contralateral paw use of cylinder test (A), and limb asymmetry score (LAS) of forehand (C) and backhand stepping test (E; p<0.05). At the second behavioural assessment (B,D,F), the L-dopa treatment effect was still significant in cylinder and stepping test, but declined comparably in both MSA-P/SND groups so that only the group 3 showed a sustained motor improvement during dopaminergic stimulation in both motor tests (p<0.05). G-H: The 6-OHDA lesion resulted in a significant reduction of tyrosine hydroxylase positive (TH+) neurons in the ipsilateral substantia nigra pars compacta (SNc) compared to the contralateral SNc (p<0.001; G). Ipsilateral striatal volume was significantly reduced compared to the contralateral side in all groups (***p<0.001) and the QA lesion resulted in a significant reduction of ipsilateral striatal volumes in groups 1 and 2 compared to the 6-OHDA only lesioned group 3 (^§§§p<0.001; H). Abbreviations: S1…saline treatment at the first behavioural assessment, LD1…L-dopa treatment at the first behavioural assessment; S2… saline treatment at the second behavioural assessment, LD2…L-dopa treatment at the second behavioural assessment; LAS…limb asymmetry score.