Bibliographic Details
| Title: |
Dopamine D2 receptor upregulation in dorsal striatum in the LRRK2-R1441C rat model of early Parkinson's disease revealed by in vivo PET imaging. |
| Authors: |
Delgado-Goñi, Teresa1,2 (AUTHOR), Connor-Robson, Natalie1,3 (AUTHOR), Cioroch, Milena1,3 (AUTHOR), Paisey, Stephen4 (AUTHOR), Marshall, Christopher4 (AUTHOR), Lane, Emma L.5 (AUTHOR), Hauton, David6 (AUTHOR), McCullagh, James6 (AUTHOR), Magill, Peter J.1,7 (AUTHOR), Cragg, Stephanie J.1,3 (AUTHOR), Mackay, Clare E.1,2 (AUTHOR), Wade-Martins, Richard1,3 (AUTHOR), Klein, Johannes C.1,8 (AUTHOR) johannes.klein@ndcn.ox.ac.uk |
| Source: |
Scientific Reports. 5/7/2025, Vol. 15 Issue 1, p1-10. 10p. |
| Abstract: |
We conducted PET imaging with [18F]FDOPA and dopamine D2/3 receptor ligand [18F]fallypride in aged transgenic rats carrying human pathogenic LRRK2 R1441C or G2019S mutations. These rats have mild age-dependent deficits in dopamine release restricted to dorsal striatum despite no overt loss of dopamine neurons or dopamine content and demonstrate L-DOPA-responsive movement deficits. LRRK2 mutant rats displayed no deficit in [18F]FDOPA uptake, consistent with intact dopamine synthesis in striatal axons. However, LRRK2-R1441C rats demonstrated greater binding of [18F]fallypride than LRRK2-G2019S or non-transgenic controls, from a regionally selective increase in dorsal striatum. Immunocytochemical labelling post-mortem confirmed a greater density of D2 receptors in LRRK2-R1441C than other genotypes restricted to dorsal striatum, consistent with upregulation of D2-receptors as a compensatory response to the greater dopamine release deficit previously demonstrated in this genotype. These results show that [18F]fallypride PET imaging is sensitive to dysregulation of dopamine signalling in the LRRK2-R1441C rat, revealing upregulation of D2 receptors that parallels observations in human putamen in early sporadic PD. Future studies of candidate therapies could exploit this non-invasive approach to assess treatment efficacy. [ABSTRACT FROM AUTHOR] |
|
Copyright of Scientific Reports is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Academic Search Complete |
|
Full text is not displayed to guests. |
Login for full access.
|
