title: Distinct modulation of the endocannabinoid system upon kainic acid-induced in vivo seizures and in vitro epileptiform bursting.
abstract: There is clear evidence on the neuroprotective role of the endocannabinoid (eCB) signaling cascade in various models of epilepsy. In particular, increased levels of eCBs protect against kainic acid (KA)-induced seizures. However, the molecular mechanisms underlying this effect and its age-dependence are still unknown. To clarify this issue, we investigated which step of the biosynthetic and catabolic pathways of the eCBs may be responsible for the eCB-mediated neuroprotection in the hippocampus of P14 and P56-70 KA-treated rats. We found that both anandamide and N-palmitoylethanolamine, together with their biosynthetic enzyme significantly increased in the hippocampus of younger KA-treated rats, while decreasing in adults. In contrast, the levels of the other major eCB, 2-arachidonoylglycerol, similar to its biosynthetic enzyme, were higher in the hippocampus of P56-70 compared to P14 rats. In line with these data, extracellular field recordings in CA1 hippocampus showed that enhancement of endogenous AEA and 2-AG significantly counteracted KA-induced epileptiform bursting in P56-70 and P14 rats, respectively. On the contrary, while the CB1R antagonist SR141716 per se did not affect the population spike, it did worsen KA-induced bursts, confirming increased eCB tone upon KA treatment. Altogether these data indicate an age-specific alteration of the eCB system caused by KA and provide insights for the protective mechanism of the cannabinoid system against epileptiform discharges.
authors: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, via Montpellier 1, 00133 Rome, Italy; European Center for Brain Research/Fondazione Santa Lucia, via del Fosso di Fiorano 65, 00143 Rome, Italy. Electronic address: filomena.fezza@uniroma2.it.
authors: Filomena
authors: F
authors: Fezza
authors: European Center for Brain Research/Fondazione Santa Lucia, via del Fosso di Fiorano 65, 00143 Rome, Italy; EBRI-Rita Levi Montalcini, via del Fosso di Fiorano 65, 00143 Rome, Italy.
authors: Maria C
authors: MC
authors: Marrone
authors: EBRI-Rita Levi Montalcini, via del Fosso di Fiorano 65, 00143 Rome, Italy; Department of Physiology and Pharmacology, University of Rome Sapienza, Rome, Italy.
authors: Riccardo
authors: R
authors: Avvisati
authors: Department of Biomedical Sciences, University of Teramo, Piazza A. Moro 45, 64100 Teramo, Italy.
authors: Monia
authors: M
authors: Di Tommaso
authors: European Center for Brain Research/Fondazione Santa Lucia, via del Fosso di Fiorano 65, 00143 Rome, Italy; Department of Biomedical Sciences, University of Teramo, Piazza A. Moro 45, 64100 Teramo, Italy.
authors: Mirko
authors: M
authors: Lanuti
authors: Department of Biomedical Sciences, University of Teramo, Piazza A. Moro 45, 64100 Teramo, Italy.
authors: Cinzia
authors: C
authors: Rapino
authors: European Center for Brain Research/Fondazione Santa Lucia, via del Fosso di Fiorano 65, 00143 Rome, Italy; Department of System Medicine, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy.
authors: Nicola B
authors: NB
authors: Mercuri
authors: European Center for Brain Research/Fondazione Santa Lucia, via del Fosso di Fiorano 65, 00143 Rome, Italy; Center of Integrated Research, Campus Bio-Medico University of Rome, Rome, Italy.
authors: Mauro
authors: M
authors: Maccarrone
authors: European Center for Brain Research/Fondazione Santa Lucia, via del Fosso di Fiorano 65, 00143 Rome, Italy; EBRI-Rita Levi Montalcini, via del Fosso di Fiorano 65, 00143 Rome, Italy. Electronic address: s.marinelli@ebri.it.
authors: Silvia
authors: S
authors: Marinelli
mesh_terms: D000375:Aging; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D063388:Endocannabinoids / Q000378:metabolism* / Q000494:pharmacology; D005989:Glycerides / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D007608:Kainic Acid; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; C094503:glyceryl 2-arachidonate; D007608:Kainic Acid; C078814:anandamide
keywords: Age-dependence; Endocannabinoids; Epileptiform bursting; Hippocampus; Kainic acid; Population spike; Seizures