Past, present and future of zebrafish in epilepsy research

Yaksi, Emre; Jamali, Ahmed; Verdugo, Carmen Diaz; Jurisch‐Yaksi, Nathalie

doi:10.1111/febs.15694

Cited by 46 publications

(44 citation statements)

References 148 publications

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“…Occasionally, we also observed spontaneous neuronal activity bursts of similar magnitude (Fig. 2e), potentially resembling spontaneous epileptic seizures 9,26–28 . Taken together, our results show that eaat2a -/- zebrafish brains exhibit increased excitability in responses to light stimulation and are possibly prone to epileptic seizures.…”

Section: Resultssupporting

confidence: 53%

Loss of glutamate transportereaat2aleads to aberrant neuronal excitability, recurrent epileptic seizures and hypoactivity

Hotz

Jamali

Rieser

et al. 2021

Preprint

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Astroglial excitatory amino acid transporter 2 (EAAT2, GLT-1, SLC1A2) regulates the duration and extent of neuronal excitation by removing glutamate from the synaptic cleft. Human patients with altered EAAT2 function exhibit epileptic seizures, suggesting an important role for astroglial glutamate transporters in balancing neuronal excitability. To study the impact of EAAT2 function at the neural network levels, we generated eaat2a mutant 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 brain activity was surprisingly reduced in eaat2a-/- mutant animals, which manifested in decreased locomotion, neuronal and astroglial calcium signals. Our results reveal an unexpected key role of the astroglial EAAT2a in balancing brain excitability, affecting both neuronal and astroglial network activity.

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Section: Resultssupporting

confidence: 53%

Loss of glutamate transportereaat2aleads to aberrant neuronal excitability, recurrent epileptic seizures and hypoactivity

Hotz

Jamali

Rieser

et al. 2021

Preprint

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“…To confirm our behavioral assay observations, we performed LFP recordings to assess seizure modulation by 6-GIN in larval brains [ 8 ]. Here, one-way ANOVA of LFP events detected from the optic tectum of 7 dpf larvae yielded statistically significant differences between tested groups of animals regarding the number (F(3, 41) = 42.53, p < 0.001; n = 6–16/group; Figure 5 A) and mean duration of events (F(3, 41) = 38.20, p < 0.001; n = 6–16/group; Figure 5 B).…”

Section: Resultsmentioning

confidence: 99%

“…To fulfill this gap in clinical practice, new animal models suitable for high-throughput screening of new drug leads are desired. Among them, zebrafish ( Danio rerio ) is now widely accepted by the scientific community as a valuable model for this purpose (for review, see [ 7 , 8 ]). What makes this model organism attractive for epilepsy research, among others, is its rapid development, high fecundity, and small size at the larval stage allowing for concomitant screening of several drugs within the same time frame and high genomic homology to mammals [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

6-Gingerol, a Major Constituent of Zingiber officinale Rhizoma, Exerts Anticonvulsant Activity in the Pentylenetetrazole-Induced Seizure Model in Larval Zebrafish

Gaweł

Kukuła-Koch

Banono

et al. 2021

IJMS

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Zingiber officinale is one of the most frequently used medicinal herbs in Asia. Using rodent seizure models, it was previously shown that Zingiber officinale hydroethanolic extract exerts antiseizure activity, but the active constituents responsible for this effect have not been determined. In this paper, we demonstrated that Zingiber officinale methanolic extract exerts anticonvulsant activity in the pentylenetetrazole (PTZ)-induced hyperlocomotion assay in larval zebrafish. Next, we isolated 6-gingerol (6-GIN)—a major constituent of Zingiber officinale rhizoma. We observed that 6-GIN exerted potent dose-dependent anticonvulsant activity in the PTZ-induced hyperlocomotion seizure assay in zebrafish, which was confirmed electroencephalographically. To obtain further insight into the molecular mechanisms of 6-GIN antiseizure activity, we assessed the concentration of two neurotransmitters in zebrafish, i.e., inhibitory γ-aminobutyric acid (GABA) and excitatory glutamic acid (GLU), and their ratio after exposure to acute PTZ dose. Here, 6-GIN decreased GLU level and reduced the GLU/GABA ratio in PTZ-treated fish compared with only PTZ-bathed fish. This activity was associated with the decrease in grin2b, but not gabra1a, grin1a, gria1a, gria2a, and gria3b expression in PTZ-treated fish. Molecular docking to the human NR2B-containing N-methyl-D-aspartate (NMDA) receptor suggests that 6-GIN might act as an inhibitor and interact with the amino terminal domain, the glutamate-binding site, as well as within the ion channel of the NR2B-containing NMDA receptor. In summary, our study reveals, for the first time, the anticonvulsant activity of 6-GIN. We suggest that this effect might at least be partially mediated by restoring the balance between GABA and GLU in the epileptic brain; however, more studies are needed to prove our hypothesis.

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“…The use of zebrafish models of epilepsy is rapidly increasing, and recent studies conducted using these models make a good case for their potential [94]. Combining their use with 2PI is an exciting prospect that may aid our understanding of the different aspects of epilepsy.…”

Section: Zebrafish Models Of Epilepsymentioning

confidence: 99%

Two-Photon Imaging to Unravel the Pathomechanisms Associated with Epileptic Seizures: A Review

et al. 2021

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Despite extensive research, the exact pathomechanisms associated with epileptic seizure formation and propagation have not been elucidated completely. Two-photon imaging (2PI) is a fluorescence-based microscopy technique that, over the years, has been used to evaluate pathomechanisms associated with epileptic seizures and epilepsy. Here, we review previous applications of 2PI in epilepsy. A systematic search was performed in multiple literature databases. We identified 38 publications that applied 2PI in epilepsy research. These studies described models of epileptic seizure propagation; anatomical changes and functional alterations of microglia, astrocytes, and neurites; and neurometabolic effects that accompany seizures. Moreover, various neurovascular alterations that accompany seizure onset and ictal events, such as blood vessel responses, have been visualized using 2PI. Lastly, imaging and quantitative analysis of oxidative stress and the aggregation of lipofuscin in the neurovasculature have been accomplished with 2PI. Cumulatively, these papers and their reported findings demonstrate that 2PI is an especially well-suited imaging technique in the domain of epilepsy research, and these studies have significantly improved our understanding of the disorder. The application of 2PI provides ample possibilities for future research, most interestingly on human brains, while also stretching beyond the field of epilepsy.

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Past, present and future of zebrafish in epilepsy research

Cited by 46 publications

References 148 publications

Loss of glutamate transportereaat2aleads to aberrant neuronal excitability, recurrent epileptic seizures and hypoactivity

Loss of glutamate transportereaat2aleads to aberrant neuronal excitability, recurrent epileptic seizures and hypoactivity

6-Gingerol, a Major Constituent of Zingiber officinale Rhizoma, Exerts Anticonvulsant Activity in the Pentylenetetrazole-Induced Seizure Model in Larval Zebrafish

Two-Photon Imaging to Unravel the Pathomechanisms Associated with Epileptic Seizures: A Review

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