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Neurochem Int. 2012 Feb;60(3):286-91. doi: 10.1016/j.neuint.2011.11.004. Epub 2011 Dec 28.

[¹²⁵I]SD-7015 reveals fine modalities of CB₁ cannabinoid receptor density in the prefrontal cortex during progression of Alzheimer's disease.

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1
Department of Neurology, University of Debrecen, H-4012 Debrecen, Hungary.

Abstract

The cannabinoid type-1 receptor (CB₁R) is one of the most abundant members of the G protein-coupled receptor family in the central nervous system. Once activated by their cognate ligands, endocannabinoids, CB₁Rs generally limit the timing of neurotransmitter release at many cortical synapses. Prior studies have indicated the involvement of CB₁R in neurodegeneration and in various neuronal insults, with an emphasis on their neuroprotective role. In the present study we used a novel selective CB₁R radioligand to investigate regional variations in CB₁R ligand binding as a factor of progressive Braak tau pathology in the frontal cortex of Alzheimer's disease (AD) patients. The frontal cortex was chosen for this study due to the high density of CB₁Rs and their well-characterized involvement in the progression of AD. Post-mortem prefrontal cortex samples from AD patients from Braak stages I to VI and controls were subjected to CB₁R autoradiography with [¹²⁵I]SD-7015 as radioligand. Regional concentration of [¹²⁵I]SD-7015, corresponding to, and thereby representing, regional CB₁R densities, were expressed in fM/g_tissue. The results show that CB₁R density inversely correlates with Braak tau pathology with the following tendency: controls <AD Braak stage V-VI <AD Braak stage III-IV <AD Braak stage I-II. Differences were significant between control and AD Braak stage I-II groups, as well as between controls and the AD group comprising all Braak stages. These findings indicate an up-regulation of the tissue binding of the selective CB₁R radioligand [¹²⁵I]SD7015 in human brains, allowing the detection of fine modalities of receptor expression and radioligand binding during the progression of AD.

PMID:
22222721
PMCID:
PMC4180663
DOI:
10.1016/j.neuint.2011.11.004
[Indexed for MEDLINE]
Free PMC Article
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