glyceryl-2-arachidonate and Brain-Diseases

Prion diseases are neurodegenerative disorders characterized by deposition of the pathological prion protein (PrPsc) within the brain of affected humans and animals. Microglial cell activation is a common feature of prion diseases; alterations of various neurotransmitter systems and neurotransmission have been also reported. Owing to its ability to modulate both neuroimmune responses and neurotransmission, it was of interest to study the brain endocannabinoid system in a prion-infected mouse model. The production of the endocannabinoid, 2-arachidonoyglycerol (2-AG), was enhanced 10 weeks post-infection, without alteration of the other endocannabinoid, anandamide. The CB2 receptor expression was up-regulated in brains of prion-infected mice as early as 10 weeks and up to 32 weeks post-infection whereas the mRNAs of other cannabinoid receptors (CBRs) remain unchanged. The observed alterations of the endocannabinoid system were specific for prion infection since no significant changes were observed in the brain of prion-resistant mice, that is, mice devoid of the Prnp gene. Our study highlights important alterations of the endocannabinoid system during early stages of the disease long before the clinical signs of the disease.

Topics: Animals; Arachidonic Acids; Brain Diseases; Cannabinoid Receptor Modulators; Cell Line; Cells, Cultured; Disease Models, Animal; Endocannabinoids; Glycerides; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Prion Diseases; Receptor, Cannabinoid, CB2; Receptors, Cannabinoid; Up-Regulation

Endocannabinoids have paradoxical effects on the mammalian nervous system: Sometimes they block neuronal excitability and other times they augment it. In their Perspective, Mechoulam and Lichtman discuss new work (Marsicano et al.) showing that activation of the cannabinoid receptor CB1 by the endocannabinoid anandamide protects against excitotoxic damage in a mouse model of kainic acid-induced epilepsy.

Topics: Animals; Anticonvulsants; Arachidonic Acids; Brain; Brain Diseases; Cannabidiol; Cannabinoid Receptor Modulators; Cannabinoids; Convulsants; Dronabinol; Endocannabinoids; Epilepsy; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; gamma-Aminobutyric Acid; Glutamic Acid; Glycerides; Humans; Kainic Acid; Mice; Neurons; Neuroprotective Agents; Polyunsaturated Alkamides; Rats; Receptors, Cannabinoid; Receptors, Drug; Signal Transduction