In vivo type 1 cannabinoid receptor mapping in the 6-hydroxydopamine lesion rat model of Parkinson's disease

被引：23

作者：

Casteels, Cindy ^{[1
,2
,3
]}

Lauwers, Erwin ^{[3
,4
]}

Baitar, Abdelbari ^{[1
,2
]}

Bormans, Guy ^{[3
,5
]}

Baekelandt, Veerle ^{[3
,4
]}

Van Laere, Koen ^{[1
,2
,3
]}

机构：

[1] Katholieke Univ Leuven, Div Nucl Med, Leuven, Belgium

[2] Univ Hosp Leuven, Div Nucl Med, Louvain, Belgium

[3] Katholieke Univ Leuven, Mol Small Anim Imaging Ctr, Louvain, Belgium

[4] Katholieke Univ Leuven, Lab Neurobiol & Gene Therapy, Louvain, Belgium

[5] Katholieke Univ Leuven, Lab Radiopharm, Louvain, Belgium

来源：

BRAIN RESEARCH | 2010年 / 1316卷

关键词：

Type 1 cannabinoid receptor; Small-animal PET; Parkinson's disease; Statistical parametric mapping; F-18]MK-9470; MESSENGER-RNA LEVELS; CB1; RECEPTOR; BASAL-GANGLIA; SUBSTANTIA-NIGRA; SENSORIMOTOR INTEGRATION; DOPAMINE NEURONS; CAUDATE-PUTAMEN; BRAIN; ACTIVATION; STRIATUM;

D O I：

10.1016/j.brainres.2009.12.026

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Type 1 cannabinoid (CB1) receptors are expressed in high concentrations in the central nervous system, including the basal ganglia, and could have direct or indirect effects on motor behavior through modulation of dopaminergic, glutamatergic and GABA-ergic neurotransmission. Using the CB1 receptor radioligand [F-18]MK-9470 and small-animal PET, we investigated for the first time in vivo cerebral changes in [F-18]MK-9470 binding in the 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease (PD), parallel to dopamine transporter (DAT) imaging, tyrosine hydroxylase (TH) staining, and behavioral measurements. In the 6-OHDA model, relative [F-18]MK-9470 PET binding decreased in the contralateral cerebellum (-9%, p<0.0004) and caudate-putamen bilaterally (ipsilateral -8%, contralateral -7%; p=0.001 and p<0.0003, respectively). The number of TH+ neurons in the substantia nigra was inversely correlated to CB1 receptor binding in the ipsilateral cerebellum (p=1.10(-6)). The behavioral outcome was positively related to regional CB1 receptor binding in the contralateral somatosensory cortex (p =4.10(-6)). in vivo [(18F)]MK-9470 PET imaging points to changes in endocannabinoid transmission, specifically for CB1 receptors in the 6-OHDA model of PD, with mainly involvement of the caudate-putamen, but also distant regions of the motor circuitry, including the cerebellum and somatosensory cortex. (C) 2009 Elsevier B.V. All rights reserved.

引用

页码：153 / 162

页数：10

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