Regional distribution and effects of postmortal delay on endocannabinoid content of the human brain.
Tissue levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) have been determined in 16 regions and nuclei from human brains, using liquid chromatography/in-line mass spectrometry. Measurements in brain samples stored at -80 degrees C for 2 months to 13 years indicated that endocannabinoids were stable under such conditions. In contrast, the postmortal delay had a strong effect on brain endocannabinoid levels, as documented in brain samples microdissected and frozen 1-6 h postmortem, and in neurosurgical samples 0, 5, 30, 60, 180 and 360 min after their removal from the brain. The tissue levels of AEA increased continuously and in a region-dependent manner from 1 h after death, increasing about sevenfold by 6 h postmortem. In contrast, concentrations of 2-AG, which were 10-100 times higher in human brain regions than those of AEA, rapidly declined: within the first hour, 2-AG levels dropped to 25-35% of the initial ('0 min') value, thereafter they remained relatively stable. As analyzed in samples removed 1-1.5 h postmortem, AEA levels ranged from a high of 96.3 fmol/mg tissue in the nucleus accumbens to a low of 25.0 fmol/mg in the cerebellum. 2-AG levels varied eightfold, from 8.6 pmol/mg in the lateral hypothalamus to 1.1 pmol/mg in the nucleus accumbens. Relative levels of AEA and 2-AG varied from region to region, with the 2-AG:AEA ratio being high in the sensory spinal trigeminal nucleus (140:1), the spinal dorsal horn (136:1) and the lateral hypothalamus (98:1) and low in the nucleus accumbens (16:1) and the striatum (31:1). The results highlight the pitfall of analyzing endocannabinoid content in brain samples of variable postmortal delay, and document differential distribution of the two main endocannabinoids in the human brain.
Palkovits
M
M
Neuromorphological and Neuroendocrine Research Laboratory of the Semmelweis University and the Hungarian Academy of Sciences, 1094 Budapest, Hungary. palkovits@ana.sote.hu
Harvey-White
J
J
Liu
J
J
Kovacs
Z S
ZS
Bobest
M
M
Lovas
G
G
Bagó
A G
AG
Kunos
G
G
D001095:Arachidonic Acids / Q000378:metabolism*; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D001923:Brain Chemistry / Q000502:physiology*; D002853:Chromatography, Liquid / Q000379:methods; D063388:Endocannabinoids; D005260:Female; D005989:Glycerides / Q000378:metabolism*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D042282:Microdissection; D053284:Polyunsaturated Alkamides / Q000378:metabolism*; D011180:Postmortem Changes; D013997:Time Factors
D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; C094503:glyceryl 2-arachidonate; C078814:anandamide