Scholarlink

<p>We conducted PET imaging with [<sup>18</sup>F]FDOPA and dopamine D2/3 receptor ligand [<sup>18</sup>F]fallypride in aged transgenic rats carrying human pathogenic <i>LRRK2</i> 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.</p><p><i>LRRK2</i> mutant rats displayed no deficit in [<sup>18</sup>F]FDOPA uptake, consistent with intact dopamine synthesis in striatal axons. However, <i>LRRK2</i>-R1441C rats demonstrated greater binding of [<sup>18</sup>F]fallypride than <i>LRRK2</i>-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 <i>LRRK2</i>-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.</p><p>These results show that [<sup>18</sup>F]fallypride PET imaging is sensitive to dysregulation of dopamine signalling in the <i>LRRK2</i>-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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Dopamine D2 receptor upregulation in dorsal striatum in the LRRK2-R1441C rat model of early Parkinson’s disease revealed by in vivo PET imaging

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月7日

查看全文
  • Teresa Delgado-Goñi,
  • Natalie Connor-Robson,
  • Milena Cioroch,
  • Stephen Paisey,
  • Christopher Marshall,
  • Emma L. Lane,
  • David Hauton,
  • James McCullagh,
  • Peter J. Magill,
  • Stephanie J. Cragg,
  • Clare E. Mackay,
  • Richard Wade-Martins,
  • Johannes C. Klein

摘要

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.