Dynamic Changes of CB1-receptor Expression in Hippocampi of Epileptic Mice and Humans

Overview

Journal Epilepsia

Specialty Neurology

Date 2010 Jul 13

PMID 20618415

Citations 39

Authors

Zsofia Magloczky

Kinga Toth

Rita Karlocai

Sara Nagy

Lorand Eross

Sandor Czirjak

Janos Vajda

Gyorgy Rasonyi

Anna Kelemen

Vera Juhos

Peter Halasz

Ken Mackie

Tamas F Freund

Affiliations

Soon will be listed here.

Abstract

The endocannabinoid system plays a central role in retrograde synaptic communication, and controls both glutamatergic and gamma-aminobutyric acid (GABA)ergic transmission via type 1 cannabinoid (CB1) receptor. Both in sclerotic human hippocampi and in the chronic phase of pilocarpine-induced epilepsy in mice with sclerosis, CB1-receptor-positive interneuron somata were preserved both in the dentate gyrus and in the CA1 area, and the density of CB1-immunostained fibers increased considerably in the dentate molecular layer. This suggests that, although CB1 receptors are known to be reduced in density on glutamatergic axons, the CB1-receptor-expressing GABAergic axons sprout, or there is an increase of CB1-receptor levels on these fibers. The changes of CB1 immunostaining in association with the GABAergic inhibitory system appear to correlate with the severity of pyramidal cell loss in the CA1 subfield. These results confirm the involvement of the endocannabinoid system associated with GABAergic transmission in human temporal lobe epilepsy (TLE), as well as in the chronic phase of the pilocarpine model in mice. Pharmacotherapy aimed at the modulation of endocannabinoid-mediated retrograde synaptic signaling should take into account the opposite change in CB1-receptor expression observed on glutamatergic versus GABAergic axon terminals.

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References

Falenski K, Blair R, Sim-Selley L, Martin B, DeLorenzo R . Status epilepticus causes a long-lasting redistribution of hippocampal cannabinoid type 1 receptor expression and function in the rat pilocarpine model of acquired epilepsy. Neuroscience. 2007; 146(3):1232-44. PMC: 2617754. DOI: 10.1016/j.neuroscience.2007.01.065. View

Niehaus J, Liu Y, Wallis K, Egertova M, Bhartur S, Mukhopadhyay S . CB1 cannabinoid receptor activity is modulated by the cannabinoid receptor interacting protein CRIP 1a. Mol Pharmacol. 2007; 72(6):1557-66. DOI: 10.1124/mol.107.039263. View

Hajos N, Ledent C, Freund T . Novel cannabinoid-sensitive receptor mediates inhibition of glutamatergic synaptic transmission in the hippocampus. Neuroscience. 2001; 106(1):1-4. DOI: 10.1016/s0306-4522(01)00287-1. View

Katona I, Sperlagh B, Magloczky Z, SANTHA E, Kofalvi A, Czirjak S . GABAergic interneurons are the targets of cannabinoid actions in the human hippocampus. Neuroscience. 2000; 100(4):797-804. DOI: 10.1016/s0306-4522(00)00286-4. View

Wallace M, Blair R, Falenski K, Martin B, DeLorenzo R . The endogenous cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy. J Pharmacol Exp Ther. 2003; 307(1):129-37. DOI: 10.1124/jpet.103.051920. View

Wittner L, Eross L, Czirjak S, Halasz P, Freund T, Magloczky Z . Surviving CA1 pyramidal cells receive intact perisomatic inhibitory input in the human epileptic hippocampus. Brain. 2004; 128(Pt 1):138-52. DOI: 10.1093/brain/awh339. View

Marsicano G, Goodenough S, Monory K, Hermann H, Eder M, Cannich A . CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science. 2003; 302(5642):84-8. DOI: 10.1126/science.1088208. View

Turski W, Cavalheiro E, Bortolotto Z, Mello L, Schwarz M, Turski L . Seizures produced by pilocarpine in mice: a behavioral, electroencephalographic and morphological analysis. Brain Res. 1984; 321(2):237-53. DOI: 10.1016/0006-8993(84)90177-x. View

Monory K, Massa F, Egertova M, Eder M, Blaudzun H, Westenbroek R . The endocannabinoid system controls key epileptogenic circuits in the hippocampus. Neuron. 2006; 51(4):455-66. PMC: 1769341. DOI: 10.1016/j.neuron.2006.07.006. View

10.

Shafaroodi H, Samini M, Moezi L, Homayoun H, Sadeghipour H, Tavakoli S . The interaction of cannabinoids and opioids on pentylenetetrazole-induced seizure threshold in mice. Neuropharmacology. 2004; 47(3):390-400. DOI: 10.1016/j.neuropharm.2004.04.011. View

11.

Racine R . Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol. 1972; 32(3):281-94. DOI: 10.1016/0013-4694(72)90177-0. View

12.

Mackie K . Distribution of cannabinoid receptors in the central and peripheral nervous system. Handb Exp Pharmacol. 2006; (168):299-325. DOI: 10.1007/3-540-26573-2_10. View

13.

Magloczky Z, Freund T . Impaired and repaired inhibitory circuits in the epileptic human hippocampus. Trends Neurosci. 2005; 28(6):334-40. DOI: 10.1016/j.tins.2005.04.002. View

14.

Ludanyi A, Eross L, Czirjak S, Vajda J, Halasz P, Watanabe M . Downregulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus. J Neurosci. 2008; 28(12):2976-90. PMC: 6670708. DOI: 10.1523/JNEUROSCI.4465-07.2008. View

15.

Chen K, Ratzliff A, Hilgenberg L, Gulyas A, Freund T, Smith M . Long-term plasticity of endocannabinoid signaling induced by developmental febrile seizures. Neuron. 2003; 39(4):599-611. DOI: 10.1016/s0896-6273(03)00499-9. View

16.

Katona I, Sperlagh B, Sik A, Kafalvi A, Vizi E, Mackie K . Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons. J Neurosci. 1999; 19(11):4544-58. PMC: 6782612. View

17.

Hajos N, Katona I, Naiem S, Mackie K, Ledent C, Mody I . Cannabinoids inhibit hippocampal GABAergic transmission and network oscillations. Eur J Neurosci. 2000; 12(9):3239-49. DOI: 10.1046/j.1460-9568.2000.00217.x. View

18.

Toth K, Wittner L, Urban Z, Doyle W, Buzsaki G, Shigemoto R . Morphology and synaptic input of substance P receptor-immunoreactive interneurons in control and epileptic human hippocampus. Neuroscience. 2006; 144(2):495-508. PMC: 2753206. DOI: 10.1016/j.neuroscience.2006.09.039. View

19.

Magloczky Z, Halasz P, Vajda J, Czirjak S, Freund T . Loss of Calbindin-D28K immunoreactivity from dentate granule cells in human temporal lobe epilepsy. Neuroscience. 1997; 76(2):377-85. DOI: 10.1016/s0306-4522(96)00440-x. View

20.

Mackie K . Signaling via CNS cannabinoid receptors. Mol Cell Endocrinol. 2008; 286(1-2 Suppl 1):S60-5. PMC: 2435200. DOI: 10.1016/j.mce.2008.01.022. View