| RRC ID |
77054
|
| 著者 |
Kinboshi M, Shimizu S, Tokudome K, Mashimo T, Serikawa T, Ito H, Takahashi R, Ikeda A, Ohno Y.
|
| タイトル |
Imbalance of glutamatergic and GABAergic neurotransmission in audiogenic seizure-susceptible Leucine-rich glioma-inactivated 1 (Lgi1)-mutant rats.
|
| ジャーナル |
Heliyon
|
| Abstract |
Leucine-rich glioma-inactivated 1 (LGI1) was identified as a causative gene of autosomal dominant lateral temporal lobe epilepsy. We previously reported that Lgi1-mutant rats carrying a missense mutation (L385R) showed audiogenic seizure-susceptibility. To explore the pathophysiological mechanisms underlying Lgi1-related epilepsy, we evaluated changes in glutamate and GABA release in Lgi1-mutant rats. Acoustic priming (AP) for audiogenic seizure-susceptibility was performed by applying intense sound stimulation (130 dB, 10 kHz, 5 min) on postnatal day 16. Extracellular glutamate and GABA levels in the hippocampus CA1 region were evaluated at 8 weeks of age, using in vivo microdialysis techniques. Under naïve conditions without AP, glutamate and GABA release evoked by high-K+ depolarization was more prominent in Lgi1-mutant than in wild-type (WT) rats. The AP treatment on day 16 significantly increased basal glutamate levels and depolarization-induced glutamate release both in Lgi1-mutant and WT rats, yielding greater depolarization-induced glutamate release in Lgi1-mutant rats. On the other hand, the AP treatment enhanced depolarization-induced GABA release only in WT rats, and not in Lgi1-mutant rats, illustrating reduced GABAergic neurotransmission in primed Lgi1-mutant rats. The present results suggest that enhanced glutamatergic and reduced GABAergic neurotransmission are involved in the audiogenic seizure-susceptibility associated with Lgi1-mutation.
|
| 巻・号 |
9(7)
|
| ページ |
e17984
|
| 公開日 |
2023-7-1
|
| DOI |
10.1016/j.heliyon.2023.e17984
|
| PII |
S2405-8440(23)05192-7
|
| PMID |
37539249
|
| PMC |
PMC10395352
|
| リソース情報 |
| ラット |
F344-Lgi1m1Kyo (StrainID=1036) |
