Anticonvulsant effect of equilibrative nucleoside transporters 1 inhibitor in a mouse model of Dravet syndrome

There are limited therapeutic options for patients with Dravet syndrome (DS). The equilibrative nucleoside transporters 1 (ENT1) mediate both the influx and efflux of adenosine across the cell membrane exerted beneficial effects in the treatment of epilepsy. This study aimed to evaluate the anticonv...

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Published inHippocampus Vol. 34; no. 1; pp. 7 - 13
Main Authors Ho, Shih‐Yin, Chen, I‐Chun, Tsai, Che‐Wen, Chang, Kai‐Chieh, Lin, Chun‐Jung, Chern, Yijuang, Liou, Horng‐Huei
Format Journal Article
LanguageEnglish
Published Hoboken, USA John Wiley & Sons, Inc 01.01.2024
Wiley Subscription Services, Inc
Subjects
A1R
Animal models
Animals
Anticonvulsants
Anticonvulsants - pharmacology
Anticonvulsants - therapeutic use
Cell membranes
Dentate gyrus
Disease Models, Animal
ENT1
Epilepsies, Myoclonic - drug therapy
Epilepsies, Myoclonic - genetics
Epilepsies, Myoclonic - metabolism
Epilepsy
febrile seizure
Granule cells
Humans
Hyperthermia
Mice
NAV1.1 Voltage-Gated Sodium Channel - genetics
Neurons - metabolism
Nucleosides
Nucleosides - therapeutic use
patch‐clamp
Scn1a
Seizures
A1R
ENT1
patch-clamp
Scn1a
febrile seizure
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Summary:There are limited therapeutic options for patients with Dravet syndrome (DS). The equilibrative nucleoside transporters 1 (ENT1) mediate both the influx and efflux of adenosine across the cell membrane exerted beneficial effects in the treatment of epilepsy. This study aimed to evaluate the anticonvulsant effect of the ENT1 inhibitor in an animal model of DS (Scn1aE1099X/+ mice). J7 (5 mg/kg) treatment was efficacious in elevating seizure threshold in Scn1aE1099X/+ mice after hyperthermia exposure. Moreover, the J7 treatment significantly reduced the frequency of spontaneous excitatory post‐synaptic currents (sEPSCs, ~35% reduction) without affecting the amplitude in dentate gyrus (DG) granule cells. Pretreatment with the adenosine A1 receptor (A1R) antagonist, DPCPX, abolished the J7 effects on sEPSCs. These observations suggest that the J7 shows an anticonvulsant effect in hyperthermia‐induced seizures in Scn1aE1099X/+ mice. This effect possibly acts on presynaptic A1R‐mediated signaling modulation in granule cells.
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content type line 23
ISSN:1050-9631
1098-1063
1098-1063
DOI:10.1002/hipo.23584