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Fezza F.,University of Rome Tor Vergata | Fezza F.,European Center for Brain Research Fondazione Santa Lucia | Marrone M.C.,European Center for Brain Research Fondazione Santa Lucia | Avvisati R.,EBRI Rita Levi Montalcini | And 10 more authors.
Molecular and Cellular Neuroscience | Year: 2014

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. © 2014 Elsevier Inc.

PubMed | European Molecular Biology Laboratory EMBL, University College Dublin, Max Planck Institute of Molecular Cell Biology and Genetics, European Center for Brain Research Fondazione Santa Lucia and 2 more.
Type: | Journal: Scientific reports | Year: 2016

We present a method for the systematic identification of picogram quantities of new lipids in total extracts of tissues and fluids. It relies on the modularity of lipid structures and applies all-ions fragmentation LC-MS/MS and Arcadiate software to recognize individual modules originating from the same lipid precursor of known or assumed structure. In this way it alleviates the need to recognize and fragment very low abundant precursors of novel molecules in complex lipid extracts. In a single analysis of rat kidney extract the method identified 58 known and discovered 74 novel endogenous endocannabinoids and endocannabinoid-related molecules, including a novel class of N-acylaspartates that inhibit Hedgehog signaling while having no impact on endocannabinoid receptors.

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