Activation of the CB2 receptor system reverses amyloid-induced memory deficiency.
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.
Institute of Anesthesiology, Cleveland Clinic, Cleveland, OH 44195, USA.
Jiang
J
Wu
Bihua
B
Bie
Hui
H
Yang
Jijun J
JJ
Xu
David L
DL
Brown
Mohamed
M
Naguib
D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001572:Benzofurans / Q000494:pharmacology* / Q000627:therapeutic use; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D039481:CD11b Antigen / Q000187:drug effects / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000187:drug effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000187:drug effects / Q000378:metabolism; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology*; D017628:Microglia / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*
C534147:1-((3-benzyl-3-methyl-2,3-dihydro-1-benzofuran-6-yl)carbonyl)piperidine; D016229:Amyloid beta-Peptides; D001572:Benzofurans; D039481:CD11b Antigen; C469526:Cnr2 protein, rat; D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D010880:Piperidines; D043885:Receptor, Cannabinoid, CB2