FENS Forum 2006

FENS Forum 2006 - Vienna

For lectures, symposia and workshops, time indicates the beginning of the session.
For posters, authors are expected to be in attendance at their posters at the time indicated.

First author: Ludanyi, Aniko (poster)

Poster board 500 - Sun 09/07, 11:30 - Hall Y
Session 024 - Epilepsy I
Abstract A024.22, published in FENS Forum Abstracts, vol. 3, 2006.
Ref.: FENS Abstr., vol.3, A024.22, 2006

Author(s) Ludanyi A. (1), Nagy S. (1), Katarova Z. (1), Eross L. (2), Czirjak S. (2), Vajda J. (2), Halasz P. (3), Szabo G. (1), Mackie K. (4), Watanabe M. (5), Katona I. (1), Freund T. F. (1) & Magloczky Z. (1)

Addresse(s) (1) Inst. of Experimental Medicine, Hungarian Acad. Sci., Budapest, Hungary; (2) National Inst. of Neurosurgery, Budapest, Hungary; (3) National Inst. of Psychiatry and Neurology, Budapest, Hungary; (4) Dept. of Anaesthesiology, Univ. of Washington, Washington, USA; (5) Dept. of Anatomy, Hokkaido Univ. School of Med., Sapporo, Japan

Title 2-arachidonoyl-glycerol - specific changes of endocannabinoid system at glutamatergic synapses in temporal lobe epileptic (TLE) patients.

Text CB1 cannabinoid receptors are one of the most abundant receptors in the brain and are expressed by both glutamatergic principal cells and GABAergic interneurons on their terminals. Thus, dysfunction of the endocannabinoid system in epilepsy may contribute to imbalance of excitation/inhibition in the network. In animal experiments synthetic agonists, antagonists, and natural ligands of CB1 have been found to evoke or prevent epileptic seizures, whereas endocannabinoid levels were changed by seizures.
To elucidate potential chronic changes in the activity of the endocannabinoid system in human TLE, we measured the expression level of all genes identified to date as components of the cannabinoid system. Quantitative real-time PCR experiments provided evidence that mRNA level of the CB1 receptor is decreased to ~50% in non-sclerotic and to ~30% in sclerotic epileptic hippocampal tissue. Immunostaining for CB1 receptors confirmed this reduction, which was most apparent in the inner molecular layer of the dentate gyrus. Furthermore, we found a significant reduction in the level of diacylglycerol lipase alpha, the main enzyme responsible for the synthesis of the endocannabinoid 2-arachidonoyl-glycerol (2-AG) as well as in level of cannabinoid receptor interacting protein 1a, a glutamatergic cell-specific anchoring protein of CB1. In contrast, levels of the enzymes N-arachidonoylphosphatidylethanolamine phospholipase D and fatty acid amide hydrolase responsible for synthesis and degradation of the endocannabinoid anandamide, did not change significantly. Similarly, we did not observe significant alteration in the level of 2-AG degrading monoglyceride lipase.
These findings demonstrate that those elements responsible for 2-AG-mediated endocannabinoid signaling at glutamatergic synapses are selectively reduced in the epileptic human hippocampus, which may contribute to the development of excitation/inhibition imbalance in the epileptic hippocampal network.

Theme Neurological and psychiatric conditions
Epilepsy / Human studies and animal models

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Author(s)	Ludanyi A. (1), Nagy S. (1), Katarova Z. (1), Eross L. (2), Czirjak S. (2), Vajda J. (2), Halasz P. (3), Szabo G. (1), Mackie K. (4), Watanabe M. (5), Katona I. (1), Freund T. F. (1) & Magloczky Z. (1)
Addresse(s)	(1) Inst. of Experimental Medicine, Hungarian Acad. Sci., Budapest, Hungary; (2) National Inst. of Neurosurgery, Budapest, Hungary; (3) National Inst. of Psychiatry and Neurology, Budapest, Hungary; (4) Dept. of Anaesthesiology, Univ. of Washington, Washington, USA; (5) Dept. of Anatomy, Hokkaido Univ. School of Med., Sapporo, Japan
Title	2-arachidonoyl-glycerol - specific changes of endocannabinoid system at glutamatergic synapses in temporal lobe epileptic (TLE) patients.
Text	CB1 cannabinoid receptors are one of the most abundant receptors in the brain and are expressed by both glutamatergic principal cells and GABAergic interneurons on their terminals. Thus, dysfunction of the endocannabinoid system in epilepsy may contribute to imbalance of excitation/inhibition in the network. In animal experiments synthetic agonists, antagonists, and natural ligands of CB1 have been found to evoke or prevent epileptic seizures, whereas endocannabinoid levels were changed by seizures. To elucidate potential chronic changes in the activity of the endocannabinoid system in human TLE, we measured the expression level of all genes identified to date as components of the cannabinoid system. Quantitative real-time PCR experiments provided evidence that mRNA level of the CB1 receptor is decreased to ~50% in non-sclerotic and to ~30% in sclerotic epileptic hippocampal tissue. Immunostaining for CB1 receptors confirmed this reduction, which was most apparent in the inner molecular layer of the dentate gyrus. Furthermore, we found a significant reduction in the level of diacylglycerol lipase alpha, the main enzyme responsible for the synthesis of the endocannabinoid 2-arachidonoyl-glycerol (2-AG) as well as in level of cannabinoid receptor interacting protein 1a, a glutamatergic cell-specific anchoring protein of CB1. In contrast, levels of the enzymes N-arachidonoylphosphatidylethanolamine phospholipase D and fatty acid amide hydrolase responsible for synthesis and degradation of the endocannabinoid anandamide, did not change significantly. Similarly, we did not observe significant alteration in the level of 2-AG degrading monoglyceride lipase. These findings demonstrate that those elements responsible for 2-AG-mediated endocannabinoid signaling at glutamatergic synapses are selectively reduced in the epileptic human hippocampus, which may contribute to the development of excitation/inhibition imbalance in the epileptic hippocampal network.
Theme	Neurological and psychiatric conditions Epilepsy / Human studies and animal models