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[3H]-NFPS binding to the glycine transporter 1 in the hemi-parkinsonian rat brain.
- Source :
- Experimental Brain Research; May2024, Vol. 242 Issue 5, p1203-1214, 12p
- Publication Year :
- 2024
-
Abstract
- L-3,4-dihydroxyphenylalanine (L-DOPA) is the main treatment for Parkinson's disease (PD) but with long term administration, motor complications such as dyskinesia are induced. Glycine transporter 1 (GlyT1) inhibition was shown to produce an anti-dyskinetic effect in parkinsonian rats and primates, coupled with an improvement in the anti-parkinsonian action of L-DOPA. The expression of GlyT1 in the brain in the dyskinetic state remains to be investigated. Here, we quantified the levels of GlyT1 across different brain regions using [<superscript>3</superscript>H]-NFPS in the presence of Org-25,935. Brain sections were chosen from sham-lesioned rats, L-DOPA-naïve 6-hydroxydopamine (6-OHDA)-lesioned rats and 6-OHDA-lesioned rats exhibiting mild or severe abnormal involuntary movements (AIMs). [<superscript>3</superscript>H]-NFPS binding decreased in the ipsilateral and contralateral thalamus, by 28% and 41%, in 6-OHDA-lesioned rats with severe AIMs compared to sham-lesioned animals (P < 0.01 and 0.001). [<superscript>3</superscript>H]-NFPS binding increased by 21% in the ipsilateral substantia nigra of 6-OHDA-lesioned rats with severe AIMs compared to 6-OHDA-lesioned rats with mild AIMs (P < 0.05). [<superscript>3</superscript>H]-NFPS binding was lower by 19% in the contralateral primary motor cortex and by 20% in the contralateral subthalamic nucleus of 6-OHDA-lesioned rats with mild AIMs animals compared to rats with severe AIMs (both P < 0.05). The severity of AIMs scores positively correlated with [<superscript>3</superscript>H]-NFPS binding in the ipsilateral substantia nigra (P < 0.05), ipsilateral entopeduncular nucleus (P < 0.05) and contralateral primary motor cortex (P < 0.05). These data provide an anatomical basis to explain the efficacy of GlyT1 inhibitors in dyskinesia in PD. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00144819
- Volume :
- 242
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Experimental Brain Research
- Publication Type :
- Academic Journal
- Accession number :
- 177112381
- Full Text :
- https://doi.org/10.1007/s00221-024-06815-w