Type-1 cannabinoid receptor activity during Alzheimer's disease progression

J Alzheimers Dis. 2014;42(3):761-6. doi: 10.3233/JAD-140492.

Abstract

The activity of CB1 cannabinoid receptors was studied in postmortem brain samples of Alzheimer's disease (AD) patients during clinical deterioration. CB1 activity was higher at earlier AD stages in limited hippocampal areas and internal layers of frontal cortex, but a decrease was observed at the advanced stages. The pattern of modification appears to indicate initial hyperactivity of the endocannabinoid system in brain areas that lack classical histopathological markers at earlier stages of AD, indicating an attempt to compensate for the initial synaptic impairment, which is then surpassed by disease progression. These results suggest that initial CB1 stimulation might have therapeutic relevance.

Keywords: Alzheimer's disease; G-protein; cannabinoid receptors; functional autoradiography; ligand binding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / pathology*
  • Analgesics / pharmacology
  • Benzoxazines / pharmacology
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Brain / metabolism*
  • Brain / pathology
  • Cyclohexanols / pharmacokinetics
  • Diagnosis
  • Disease Progression
  • Female
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacokinetics
  • Humans
  • Isotopes / pharmacokinetics
  • Male
  • Morpholines / pharmacology
  • Naphthalenes / pharmacology
  • Radionuclide Imaging
  • Receptor, Cannabinoid, CB1 / drug effects
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Statistics, Nonparametric

Substances

  • Analgesics
  • Benzoxazines
  • Cyclohexanols
  • Isotopes
  • Morpholines
  • Naphthalenes
  • Receptor, Cannabinoid, CB1
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol