Synaptic localization of the enzymatic machinery responsible for 2-arachidonoylglycerol synthesis and degradation in the human hippocampus

Abstract

Event Abstract Back to Event Synaptic localization of the enzymatic machinery responsible for 2-arachidonoylglycerol synthesis and degradation in the human hippocampus Anikó Ludányi1*, Zsófia Maglóczky1, Ken Mackie2, Tamás Freund1 and István Katona1 1 Hungarian Academy of Sciences, Institute of Experimental Medicine, Hungary 2 Indiana University, Department of Psychological and Brain Sciences, United States Endocannabinoid signaling is involved in several forms of synaptic plasticity in the brain. Although molecular architecture of the endocannabinoid system has already been revealed in rodents, whether it is an evolutionarily conserved feature of hippocampal excitatory synapses has remained elusive. To address this issue, we studied the subcellular localization of enzymes synthesizing and degrading endocannabinoid 2-arachidonoylglycerol (2-AG) in the human hippocampus (n = 6). At the light microscopic level, immunostaining for diacylglycerol lipase-alpha (DGL-alpha), the main biosynthetic enzyme of 2-AG, visualized a similar staining pattern in post mortem human hippocampus as found earlier in the rodent. At higher magnification, DGL-alpha-immunopositive puncta throughout the neuropil outlined immunonegative main apical dendrites of pyramidal cells. Further electron microscopic investigations revealed that labeling corresponds to the accumulation of DGL-alpha in dendritic spine heads. Notably, immunostaining for 2-AG’s predominant degrading enzyme, monoacylglycerol lipase (MGL) resulted in very similar staining pattern at the light microscopic level. However, further electron microscopic analysis revealed that MGL was enriched in axon terminals, but not in spine heads. Our results suggest that formation of 2-AG by DGL-alpha occurs in postsynaptic dendritic spines, and after acting on presynaptic CB1 cannabinoid receptors, it is degraded in axon terminals by MGL. Taken together, these findings show that the localization of metabolic enzymes involved in synaptic 2-AG signaling is similar in rodent and human suggesting an evolutionarily conserved feature of excitatory synapses. Moreover, the molecular architecture of endocannabinoid signaling seems to be precisely designed to subserve retrograde regulation of synaptic neurotransmission and likely has a fundamental physiological role as a negative feed-back signal protecting synapses from excessive presynaptic activity. Conference: IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010. Presentation Type: Poster Presentation Topic: Cellular neuroscience Citation: Ludányi A, Maglóczky Z, Mackie K, Freund T and Katona I (2010). Synaptic localization of the enzymatic machinery responsible for 2-arachidonoylglycerol synthesis and degradation in the human hippocampus. Front. Neurosci. Conference Abstract: IBRO International Workshop 2010. doi: 10.3389/conf.fnins.2010.10.00091 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 22 Apr 2010; Published Online: 22 Apr 2010. * Correspondence: Anikó Ludányi, Hungarian Academy of Sciences, Institute of Experimental Medicine, Budapest, Hungary, ludanyi@koki.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Anikó Ludányi Zsófia Maglóczky Ken Mackie Tamás Freund István Katona Google Anikó Ludányi Zsófia Maglóczky Ken Mackie Tamás Freund István Katona Google Scholar Anikó Ludányi Zsófia Maglóczky Ken Mackie Tamás Freund István Katona PubMed Anikó Ludányi Zsófia Maglóczky Ken Mackie Tamás Freund István Katona Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.