Revisiting the role of neurotransmitters in epilepsy: An updated review

Akyüz, Enes; Polat, Ayse Kristina; Eroğlu, Ece; Küllü, İ̇rem; Angelopoulou, Efthalia; Paudel, Yam Nath

doi:10.1016/j.lfs.2020.118826

Cited by 155 publications

(89 citation statements)

References 233 publications

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“…The inhibitory activity on seizure paroxysmal behavior in zebrafish larvae was confirmed by LFP recordings in larval brains. To gain further insight into the anticonvulsant activity of 6-GIN, we measured the concentration of two neurotransmitters, i.e., inhibitory γ-aminobutyric acid (GABA) and excitatory glutamic acid (GLU), which are known to be dysregulated in epileptic patients [ 27 , 28 , 29 ]. Additionally, we measured the concentration of serotonin (5-HT) [ 27 , 28 ] and dopamine (DA) [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

“…To gain further insight into the anticonvulsant activity of 6-GIN, we measured the concentration of two neurotransmitters, i.e., inhibitory γ-aminobutyric acid (GABA) and excitatory glutamic acid (GLU), which are known to be dysregulated in epileptic patients [ 27 , 28 , 29 ]. Additionally, we measured the concentration of serotonin (5-HT) [ 27 , 28 ] and dopamine (DA) [ 29 , 30 ]. Next, using quantitative real-time polymerase chain reaction (qRT-PCR), we analyzed the expression of a few genes encoding neurotransmitter receptors (namely gabra1a , grin1a , grin2b, gria1a, gria2a , and gria3b ) to quantify possible changes in expression.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 99%

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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“…However, the imbalance in excitatory and inhibitory neurotransmission in the brain possibly contributes to the generation and propagation of seizures. In addition, alterations in the ion channels' expression in the brain are considered as a plausible underlying cause [111][112][113].…”

Section: Chrysin In Epilepsymentioning

confidence: 99%

Neuroprotective Potential of Chrysin: Mechanistic Insights and Therapeutic Potential for Neurological Disorders

Mishra

Bandopadhyay

et al. 2021

Molecules

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Chrysin, a herbal bioactive molecule, exerts a plethora of pharmacological effects, including anti-oxidant, anti-inflammatory, neuroprotective, and anti-cancer. A growing body of evidence has highlighted the emerging role of chrysin in a variety of neurological disorders, including Alzheimer’s and Parkinson’s disease, epilepsy, multiple sclerosis, ischemic stroke, traumatic brain injury, and brain tumors. Based on the results of recent pre-clinical studies and evidence from studies in humans, this review is focused on the molecular mechanisms underlying the neuroprotective effects of chrysin in different neurological diseases. In addition, the potential challenges, and opportunities of chrysin’s inclusion in the neurotherapeutics repertoire are critically discussed.

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“…Many neurotransmitters and hormones such as serotonin, norepinephrine, histamine, are involved in epilepsy. 7 Gamma-aminobutyric acid (GABA) and nicotinic acetylcholine (ACh) receptors, in particular, have been implicated. Mutations in GABA receptors have been shown to cause ER stress and ion imbalance, contributing to epileptogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, dysfunctional acetylcholine signaling has been shown to aggravate inflammation, a key feature of epilepsy. 7 Although epilepsy can occur in any region of the brain, it is known to affect the frontal lobe and the temporal lobe most commonly, particularly the hippocampus. 8 Therefore, studying the regulatory mechanisms of neurotransmitters in cortical and hippocampal regions of the brain is important in furthering our understanding of epilepsy.…”

Section: Introductionmentioning

confidence: 99%

GPR40 and Postsynaptic NMDA Receptors: A Pair Against Epilepsy

Mullangi

Shah

Nam

et al. 2021

Georgetown Scientific Research Journal

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Epilepsy is a chronic neurological condition characterized by abnormal brain activity, unusual behavior, and loss of awareness. One of the most common features is the spontaneous recurrence of unprovoked seizures that mainly affect the hippocampus and cortical regions of the brain. Although the exact cause of epilepsy is still unknown, a mix of genetic, neurological, and environmental factors play a role. A novel study by Yang et al. explores the metabotropic receptor GPR40 which is suspected to be involved in the regulation of epileptic seizures, specifically through its modulatory role on NMDA receptors in the central nervous system. Their findings suggest that GPR40 induces NMDA receptor endocytosis via direct interaction with NR2A and NR2B subunits of postsynaptic NMDA receptors. Through this mechanism, NMDA-mediated postsynaptic currents are altered, resulting in reduced seizure-like activity. This review article discusses these novel findings which not only shed light on the potential molecular mechanisms of epilepsy but also push the scientific community closer to developing a treatment for this disorder.

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Revisiting the role of neurotransmitters in epilepsy: An updated review

Cited by 155 publications

References 233 publications

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

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

Neuroprotective Potential of Chrysin: Mechanistic Insights and Therapeutic Potential for Neurological Disorders

GPR40 and Postsynaptic NMDA Receptors: A Pair Against Epilepsy

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