Signal transduction pathway activity compensates dopamine D₂/D₃ receptor density changes in Parkinson's disease: a preliminary comparative human brain receptor autoradiography study with [³H]raclopride and [³⁵S]

详细信息	查看全文 | 推荐本文 |

• 作者：Szabolcs Farkas^a ; Katalin Nagy^a ; Zhisheng Jia^b ; Tibor Hortob5 ; gyi^a ; Andrea Varrone^b ; Christer Halldin^b ; L5 ; szló ; Csiba^a ; ¹ ; Bal5 ; zs Guly5 ; s^b ; ¹ ; ^{balazs.gulyas@ki.se}
• 关键词：ARG ; autoradiography ; DAT ; dopamine transporter ; GTP纬S ; guanosine 5&prime ; -O-[gamma-thio]triphosphate ; l-DOPA ; L-3 ; 4-dihydroxyphenylalanine ; MAO-B ; Monoamine oxidase B ; MPTP ; 1-methyl-4-phenyl-1 ; 2 ; 3 ; 6-tetrahydropyridine ; OD ; optical density ; PD ; Parkinso
• 刊名：Brain Research
• 出版年：2012
• 期刊代码：8_00068993
• 类别：neu
• 出版时间：9 May, 2012
• 卷：1453
• 期：Complete
• 页码：56-63
• 文件大小：438 K

摘要

The degeneration of dopaminergic nigrostriatal pathway in Parkinson's disease (PD) results in alterations of the dopamine receptor system. In the present study we have investigated the relationship between the disease related changes of expressed dopamine D₂/D₃ receptor density and the corresponding intracellular signal transduction route in cortical and sub-cortical brain structures in the human brain.

Dopamine D₂/D₃ receptor autoradiography (ARG), using [³H]raclopride, and agonist stimulated [³⁵S]GTP纬S (guanosine 5鈥?O-[纬-thio]triphosphate) binding autoradiography have been performed in human striatum, cingulate gyrus and medial frontal gyrus samples obtained from six deceased PD patients and six age matched control subjects. Receptor densities were expressed as fmol/gram tissue protein for [³H]raclopride; agonist stimulated [³⁵S]GTP纬S binding was expressed in fmol/gram tissue and its change was expressed in percentage values above basal binding.

Our results indicate that whereas there is a decrease of the dopamine D₂/D₃ receptors in the striatum demonstrated by classical receptor autoradiography (controls and PD: 24.08 卤 2.06 fmol/gram (mean 卤 SEM) and 18.43 卤 2.82 fmol/gram, respectively; p < 0.05), the corresponding agonist stimulated [³⁵S]GTP纬S binding autoradiography shows unchanged basal [³⁵S]GTP纬S binding (controls and PD: 199 卤 17 fmol/g and 198 卤 21 fmol/g, respectively; n.s.) and, at the same time, no change in stimulation (controls and PD: 0.40 卤 4.57%and 1.51 卤 2.27%, respectively; n.s.). In cingular gyrus and medial frontal gyrus neither the dopamine D₂/D₃ receptor densities nor the [³⁵S]GTP纬S binding displayed significant differences between PD and age matched control brain samples, whereas the [³⁵S]GTP纬S binding values were markedly higher in PD.

These preliminary findings may indicate a possible compensatory mechanism in striatal regions of PD brains: the loss of the dopamine receptors in the striatum appears to be compensated by an increased post-synaptic intracellular signal transduction route activity. However, the accurate interpretation of the present findings requires detailed further studies.