Activation of the CB2 receptor system reverses amyloid-induced memory deficiency

Neurobiol Aging. 2013 Mar;34(3):791-804. doi: 10.1016/j.neurobiolaging.2012.06.011. Epub 2012 Jul 12.

Abstract

Cannabinoid type 2 (CB(2)) agonists are neuroprotective and appear to play modulatory roles in neurodegenerative processes in Alzheimer's disease. We have studied the effect of 1-((3-benzyl-3-methyl-2,3-dihydro-1-benzofuran-6-yl) carbonyl) piperidine (MDA7)-a novel selective CB(2) agonist that lacks psychoactivity-on ameliorating the neuroinflammatory process, synaptic dysfunction, and cognitive impairment induced by bilateral microinjection of amyloid-β (Aβ)(1-40) fibrils into the hippocampal CA1 area of rats. In rats injected with Aβ(1-40) fibrils, compared with the administration of intraperitoneal saline for 14 days, treatment with 15 mg/kg of intraperitoneal MDA7 daily for 14 days (1) ameliorated the expression of CD11b (microglia marker) and glial fibrillary acidic protein (astrocyte marker), (2) decreased the secretion of interleukin-1β, (3) decreased the upsurge of CB(2) receptors, (4) promoted Aβ clearance, and (5) restored synaptic plasticity, cognition, and memory. Our findings suggest that MDA7 is an innovative therapeutic approach for the treatment of Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / adverse effects*
  • Animals
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Behavior, Animal / drug effects
  • Benzofurans / pharmacology*
  • Benzofurans / therapeutic use
  • CA1 Region, Hippocampal* / cytology
  • CA1 Region, Hippocampal* / drug effects
  • CA1 Region, Hippocampal* / metabolism
  • CD11b Antigen / drug effects
  • CD11b Antigen / metabolism
  • Cognition / drug effects
  • Glial Fibrillary Acidic Protein / drug effects
  • Glial Fibrillary Acidic Protein / metabolism
  • Interleukin-1beta / drug effects
  • Interleukin-1beta / metabolism
  • Memory / drug effects*
  • Memory Disorders / drug therapy
  • Memory Disorders / etiology*
  • Microglia / cytology
  • Microglia / drug effects
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Piperidines / pharmacology*
  • Piperidines / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB2 / agonists*

Substances

  • 1-((3-benzyl-3-methyl-2,3-dihydro-1-benzofuran-6-yl)carbonyl)piperidine
  • Amyloid beta-Peptides
  • Benzofurans
  • CD11b Antigen
  • Cnr2 protein, rat
  • Glial Fibrillary Acidic Protein
  • Interleukin-1beta
  • Neuroprotective Agents
  • Piperidines
  • Receptor, Cannabinoid, CB2