Age-related changes in the endocannabinoid system in the mouse hippocampus.
Previous studies have demonstrated that the endocannabinoid system significantly influences the progression of brain ageing, and the hippocampus is one of the brain regions most vulnerable to ageing and neurodegeneration. We have further examined age-related changes in the hippocampal endocannabinoid system by measuring the levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in young and old mice from two different mouse strains. We found a decrease in 2-AG but not AEA levels in aged mice. In order to identify the cause for 2-AG level changes, we investigated the levels of several enzymes that contribute to synthesis and degradation of 2-AG in the hippocampus. We found a selective decrease in DAGLα mRNA and protein levels as well as an elevated MAGL activity during ageing. We hypothesize that the observed decrease of 2-AG levels is probably caused by changes in DAGLα expression and MAGL activity. This finding can contribute to the existing knowledge about the processes underlying selective vulnerability of the hippocampus to ageing and age-related neurodegeneration.
Institute of Molecular Psychiatry, Medical Faculty, University of Bonn, 53127 Bonn, Germany.
Anastasia
A
Piyanova
Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
Ermelinda
E
Lomazzo
Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
Laura
L
Bindila
Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
Raissa
R
Lerner
Institute of Molecular Psychiatry, Medical Faculty, University of Bonn, 53127 Bonn, Germany.
Onder
O
Albayram
Institute of Zoology, University of Bonn, 53127 Bonn, Germany.
Tim
T
Ruhl
Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
Beat
B
Lutz
Institute of Molecular Psychiatry, Medical Faculty, University of Bonn, 53127 Bonn, Germany.
Andreas
A
Zimmer
Institute of Molecular Psychiatry, Medical Faculty, University of Bonn, 53127 Bonn, Germany. Electronic address: abilkei@uni-bonn.de.
Andras
A
Bilkei-Gorzo
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D063388:Endocannabinoids / Q000378:metabolism*; D005989:Glycerides / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008071:Lipoprotein Lipase / Q000378:metabolism; D051379:Mice; D053284:Polyunsaturated Alkamides / Q000378:metabolism*
D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; C094503:glyceryl 2-arachidonate; D008071:Lipoprotein Lipase; C078814:anandamide
2-Arachidonoylglycerol; Anandamide; LC-MRM; Monoacylglycerol lipase; sn-1-diacylglycerol lipase