| RRC ID |
75648
|
| 著者 |
Hotz AL, Jamali A, Rieser NN, Niklaus S, Aydin E, Myren-Svelstad S, Lalla L, Jurisch-Yaksi N, Yaksi E, Neuhauss SCF.
|
| タイトル |
Loss of glutamate transporter eaat2a leads to aberrant neuronal excitability, recurrent epileptic seizures, and basal hypoactivity.
|
| ジャーナル |
Glia
|
| Abstract |
Astroglial excitatory amino acid transporter 2 (EAAT2, GLT-1, and SLC1A2) regulates the duration and extent of neuronal excitation by removing glutamate from the synaptic cleft. Hence, an impairment in EAAT2 function could lead to an imbalanced brain network excitability. Here, we investigated the functional alterations of neuronal and astroglial networks associated with the loss of function in the astroglia predominant eaat2a gene in zebrafish. We observed that eaat2a-/- mutant zebrafish larvae display recurrent spontaneous and light-induced seizures in neurons and astroglia, which coincide with an abrupt increase in extracellular glutamate levels. In stark contrast to this hyperexcitability, basal neuronal and astroglial activity was surprisingly reduced in eaat2a-/- mutant animals, which manifested in decreased overall locomotion. Our results reveal an essential and mechanistic contribution of EAAT2a in balancing brain excitability, and its direct link to epileptic seizures.
|
| 巻・号 |
70(1)
|
| ページ |
196-214
|
| 公開日 |
2022-1-1
|
| DOI |
10.1002/glia.24106
|
| PMID |
34716961
|
| PMC |
PMC9297858
|
| MeSH |
Animals
Astrocytes / metabolism
Epilepsy* / metabolism
Excitatory Amino Acid Transporter 2 / genetics
Excitatory Amino Acid Transporter 2 / metabolism
Glutamic Acid / metabolism
Neurons / metabolism
Seizures / genetics
Seizures / metabolism
Zebrafish* / metabolism
|
| IF |
5.984
|
| リソース情報 |
| ゼブラフィッシュ |
UAShspGCaMP6s |
