[ 125I]SD-7015 reveals fine modalities of CB 1 cannabinoid receptor density in the prefrontal cortex during progression of Alzheimer's disease

Szabolcs Farkas, Katalin Nagy, M. Palkóvits, Gábor G. Kovács, Zhisheng Jia, Sean Donohue, Vic Pike, Christer Halldin, Domokos Máthé, Tibor Harkany, Balázs Gulyás, L. Csiba

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The cannabinoid type-1 receptor (CB 1R) 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, CB 1Rs generally limit the timing of neurotransmitter release at many cortical synapses. Prior studies have indicated the involvement of CB 1R in neurodegeneration and in various neuronal insults, with an emphasis on their neuroprotective role. In the present study we used a novel selective CB 1R radioligand to investigate regional variations in CB 1R 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 CB 1Rs 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 CB 1R autoradiography with [ 125I]SD-7015 as radioligand. Regional concentration of [ 125I]SD-7015, corresponding to, and thereby representing, regional CB 1R densities, were expressed in fM/g-tissue. The results show that CB 1R density inversely correlates with Braak tau pathology with the following tendency: controls 1R radioligand [ 125I]SD7015 in human brains, allowing the detection of fine modalities of receptor expression and radioligand binding during the progression of AD.

Original languageEnglish
Pages (from-to)286-291
Number of pages6
JournalNeurochemistry International
Volume60
Issue number3
DOIs
Publication statusPublished - Feb 2012

Fingerprint

Cannabinoid Receptors
Prefrontal Cortex
Alzheimer Disease
Frontal Lobe
Pathology
Ligands
Endocannabinoids
G-Protein-Coupled Receptors
4-cyano-1-(2-iodophenyl)-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide
Autoradiography
Synapses
Neurotransmitter Agents
Central Nervous System
Brain

Keywords

  • [ I]SD7015
  • Alzheimer's disease
  • Biomarker
  • Braak classification
  • CB R
  • Endocannabinoid system
  • Human brain autoradiography
  • Molecular imaging

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

[ 125I]SD-7015 reveals fine modalities of CB 1 cannabinoid receptor density in the prefrontal cortex during progression of Alzheimer's disease. / Farkas, Szabolcs; Nagy, Katalin; Palkóvits, M.; Kovács, Gábor G.; Jia, Zhisheng; Donohue, Sean; Pike, Vic; Halldin, Christer; Máthé, Domokos; Harkany, Tibor; Gulyás, Balázs; Csiba, L.

In: Neurochemistry International, Vol. 60, No. 3, 02.2012, p. 286-291.

Research output: Contribution to journalArticle

Farkas, Szabolcs ; Nagy, Katalin ; Palkóvits, M. ; Kovács, Gábor G. ; Jia, Zhisheng ; Donohue, Sean ; Pike, Vic ; Halldin, Christer ; Máthé, Domokos ; Harkany, Tibor ; Gulyás, Balázs ; Csiba, L. / [ 125I]SD-7015 reveals fine modalities of CB 1 cannabinoid receptor density in the prefrontal cortex during progression of Alzheimer's disease. In: Neurochemistry International. 2012 ; Vol. 60, No. 3. pp. 286-291.
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