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Correlations of catecholamine metabolites and alpha-synuclein by nigral stimulation in Parkinson’s disease model rat

T. Yamamoto, R. Sakakibara, T. Uchiyama, S. Kuwabara (Chiba, Japan)

Meeting: 2025 International Congress

Keywords: Alpha-synuclein, Deep brain stimulation (DBS), Parkinson’s

Category: Parkinson's Disease: Disease mechanisms

Objective: We aimed to clarify the effects of substantia nigra (SN) stimulation on catecholamine levels and α-synuclein in PD model rats.

Background: Catecholaminergic neurons are known to degenerate in Parkinson’s disease (PD). Dopamine metabolites may contribute to α-synuclein aggregation. Our previous study found a trend of positive correlations between nigral homovanillic acid (a dopamine metabolite) and α-synuclein during nigral stimulation in normal rats.

Method: Experiments were conducted in PD model rats (n=4), created via stereotaxic injection of 6-hydroxydopamine into the medial forebrain bundle. A microdialysis probe with a tungsten electrode was inserted into the SN for electrical stimulation. Extracellular fluid was collected before, during, and after stimulation. Catecholamine levels were measured via high-performance liquid chromatography, and α-synuclein levels were measured using enzyme-linked immunosorbent assay (ELISA). Ratios of α-synuclein and catecholamine levels to their basal values were calculated for each stimulation phase.

Results: SN stimulation significantly decreased 3,4-dihydroxyphenylalanine (L-DOPA) (p<0.01), 3,4-dihydroxyphenylacetic acid (DOPAC) (p<0.01), and α-synuclein (p<0.01). Positive correlations were observed between DOPAC and α-synuclein during stimulation (r=0.67, p=0.015) (Fig.1a) and between 5-hydroxyindoleacetic acid (5-HIAA) and α-synuclein after stimulation (r=0.79, p=0.006) (Fig.1b).

Conclusion: SN stimulation alters the relationship between the dopamine metabolite DOPAC, the serotonin metabolite 5-HIAA, and α-synuclein levels.

Figure 1

Figure 1

To cite this abstract in AMA style:

T. Yamamoto, R. Sakakibara, T. Uchiyama, S. Kuwabara. Correlations of catecholamine metabolites and alpha-synuclein by nigral stimulation in Parkinson’s disease model rat [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/correlations-of-catecholamine-metabolites-and-alpha-synuclein-by-nigral-stimulation-in-parkinsons-disease-model-rat/. Accessed October 5, 2025.
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