Danish
Albanian
Arabic
Armenian
Azerbaijani
Belarusian
Bengali
Bosnian
Catalan
Czech
Danish
Deutsch
Dutch
English
Estonian
Finnish
Français
Greek
Haitian Creole
Hebrew
Hindi
Hungarian
Icelandic
Indonesian
Irish
Italian
Japanese
Korean
Latvian
Lithuanian
Macedonian
Mongolian
Norwegian
Persian
Polish
Portuguese
Romanian
Russian
Serbian
Slovak
Slovenian
Spanish
Swahili
Swedish
Turkish
Ukrainian
Vietnamese
Български
中文(简体)
中文(繁體)
PLoS ONE 2013

Epoxy fatty acids and inhibition of the soluble epoxide hydrolase selectively modulate GABA mediated neurotransmission to delay onset of seizures.

Kun registrerede brugere kan oversætte artikler
Log ind / Tilmeld
Linket gemmes på udklipsholderen
Bora Inceoglu
Dorota Zolkowska
Hyun Ju Yoo
Karen M Wagner
Jun Yang
Edward Hackett
Sung Hee Hwang
Kin Sing Stephen Lee
Michael A Rogawski
Christophe Morisseau

Nøgleord

Abstrakt

In the brain, seizures lead to release of large amounts of polyunsaturated fatty acids including arachidonic acid (ARA). ARA is a substrate for three major enzymatic routes of metabolism by cyclooxygenase, lipoxygenase and cytochrome P450 enzymes. These enzymes convert ARA to potent lipid mediators including prostanoids, leukotrienes and epoxyeicosatrienoic acids (EETs). The prostanoids and leukotrienes are largely pro-inflammatory molecules that sensitize neurons whereas EETs are anti-inflammatory and reduce the excitability of neurons. Recent evidence suggests a GABA-related mode of action potentially mediated by neurosteroids. Here we tested this hypothesis using models of chemically induced seizures. The level of EETs in the brain was modulated by inhibiting the soluble epoxide hydrolase (sEH), the major enzyme that metabolizes EETs to inactive molecules, by genetic deletion of sEH and by direct administration of EETs into the brain. All three approaches delayed onset of seizures instigated by GABA antagonists but not seizures through other mechanisms. Inhibition of neurosteroid synthesis by finasteride partially blocked the anticonvulsant effects of sEH inhibitors while the efficacy of an inactive dose of neurosteroid allopregnanolone was enhanced by sEH inhibition. Consistent with earlier findings, levels of prostanoids in the brain were elevated. In contrast, levels of bioactive EpFAs were decreased following seizures. Overall these results demonstrate that EETs are natural molecules which suppress the tonic component of seizure related excitability through modulating the GABA activity and that exploration of the EET mediated signaling in the brain could yield alternative approaches to treat convulsive disorders.

Deltag i vores
facebook-side

Den mest komplette database med medicinske urter understøttet af videnskab

  • Arbejder på 55 sprog
  • Urtekurer, der understøttes af videnskab
  • Urtegenkendelse ved billede
  • Interaktivt GPS-kort - tag urter på stedet (kommer snart)
  • Læs videnskabelige publikationer relateret til din søgning
  • Søg medicinske urter efter deres virkninger
  • Organiser dine interesser og hold dig opdateret med nyhedsundersøgelser, kliniske forsøg og patenter

Skriv et symptom eller en sygdom, og læs om urter, der kan hjælpe, skriv en urt og se sygdomme og symptomer, den bruges mod.
* Al information er baseret på offentliggjort videnskabelig forskning

Google Play badgeApp Store badge