Category: Parkinson's Disease: Pathophysiology
Objective: We examined whether levodopa-induced dyskinesia (LID) and axon terminal hypertrophy gradually develop with repeated levodopa treatment in Parkinsonian rats to prove that the hypertrophy reflects dyskinesia priming.
Background: A rat model of levodopa-induced dyskinesia (LID) showed enlarged axon terminals of striatal direct pathway neurons in the internal segment of the globus pallidus (GPi) with excessive gamma-aminobutyric acid (GABA) storage in them. Massive GABA release to GPi upon levodopa administration determines the emergence of LID.
Method: 6-hydroxydopamine-lesioned hemiparkinsonian rats were randomly allocated to receive saline injections (placebo group, 14 days; n = 4), injections of 6 mg/kg levodopa methyl ester combined with 12.5 mg/kg benserazide (levodopa-treated groups, 3-day-treatment; n = 4, 7-day-treatment; n = 4, 14-day-treatment; n = 4), or injections of 6 mg/kg levodopa methyl ester with 12.5 mg/kg benserazide and 1 mg/kg 8-hydroxy-2-(di-n-propylamino)tetralin for 14 days (8-OH-DPAT-treated group; n = 4). We evaluated abnormal involuntary movement (AIM) scores and axon terminals in the GPi.
Results: The AIM score increased with levodopa treatment, as did the hypertrophy of axon terminals in the GPi, showing an increased number of synaptic vesicles in hypertrophied terminals.
Conclusion: Increased GABA storage in axon terminals of the direct pathway neurons represents the priming process of LID.
To cite this abstract in AMA style:T. Nakamura, H. Nishijima, F. Mori, I. Kinoshita, T. Kon, C. Suzuki, K. Wakabayashi, M. Tomiyama. Axon terminal hypertrophy of striatal projection neurons with levodopa-induced dyskinesia priming [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/axon-terminal-hypertrophy-of-striatal-projection-neurons-with-levodopa-induced-dyskinesia-priming/. Accessed September 27, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/axon-terminal-hypertrophy-of-striatal-projection-neurons-with-levodopa-induced-dyskinesia-priming/