2014 Jul 24. pii: S1044-7431(14)00076-1. doi: 10.1016/j.mcn.2014.07.003. [Epub ahead of print]
Distinct modulation of the endocannabinoid system upon kainic acid-induced in vivo seizures and in vitro epileptiform bursting.
Fezza F1, Marrone MC2, Avvisati R3, Di Tommaso M4, Lanuti M5, Rapino C4, Mercuri NB6, Maccarrone M7, Marinelli S8.
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.
Copyright © 2014. Published by Elsevier Inc.
Copyright © 2014. Published by Elsevier Inc.
KEYWORDS:
Age-dependence; Endocannabinoids; Epileptiform bursting; Hippocampus; Kainic acid; Population spike; Seizures
- PMID:
- 25064144
- [PubMed – as supplied by publisher]
