Faculty Collaboration Database

Fatty acid amide hydrolase localization in the human central nervous system: an immunohistochemical study. Brain Res Mol Brain Res 2002 Apr 30;100(1-2):85-93

Date

05/15/2002

Pubmed ID

12008024

DOI

10.1016/s0169-328x(02)00167-5

Scopus ID

2-s2.0-0037197799 (requires institutional sign-in at Scopus site)   73 Citations

Abstract

Recent discoveries have opened new fields for research on the biochemistry and pharmacology of cannabinoids. Among them, and most importantly, are the characterization and molecular cloning of central and peripheral cannabinoid receptors as well as the isolation of the first putative endogenous ligands that bind to them, anandamide and 2-arachidonylglycerol. The enzyme that degrades these so-called "endocannabinoids" is an integral membrane protein, fatty acid amide hydrolase. Its distribution and biochemistry in rat brain suggest that it plays a critical role in the regulation of the endocannabinoid system. However, few data exist regarding its distribution and mechanism of action in human tissues. To that end, we have studied its cellular distribution in the human central nervous system by immunohistochemistry. Using an affinity-purified antibody, we report that fatty acid amide hydrolase is localized to specific and well-delimited cell populations, including cortical pyramidal neurons, subcortical white matter astrocytes, striatal and striatoefferent projecting neurons, hypothalamic and midbrain nuclei, granular and molecular layers of the cerebellum, Purkinje neurons, dentate cerebellar nucleus, inferior olivary nuclei and others. This distribution resembles that of the central cannabinoid receptors as well as that of the enzyme distribution in the rat brain. In summary, the cellular localization of the degradative enzyme of the endogenous cannabinoid ligands in human central nervous system reveals its presence on both neuronal and glial elements and shows a significant overlapping with that of central cannabinoid receptors, mainly in areas related with motor control, confirming the notion that the endocannabinoid system plays a critical role in the control of movement.

Author List

Romero J, Hillard CJ, Calero M, Rábano A

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Amidohydrolases
Arachidonic Acids
Astrocytes
Brain
Cannabinoid Receptor Modulators
Cannabinoids
Central Nervous System
Endocannabinoids
Female
Glycerides
Humans
Immunohistochemistry
Male
Neurons
Polyunsaturated Alkamides
Receptors, Cannabinoid
Receptors, Drug
Spinal Cord