Decreased serotonin synthesis is involved in seizure-induced respiratory arrest in DBA/1 mice

Chen, Qinglan; Tian, Fafa; Yue, Qiang; Zhan, Qimin; Wang, Mian; Xiao, Bo; Zeng, Chang

doi:10.1097/wnr.0000000000001287

Cited by 7 publications

(21 citation statements)

References 24 publications

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“…All DBA/1 mice (from PND 26–28) were subjected to an acoustic stimulation paradigm and induced daily for three consecutive days (each interval was more than 24 h) to evoke AGSz and S-IRA ( 6 , 12 ). Briefly, each mouse was placed in a transparent plastic chamber and stimulated continuously with a 110 dB electric bell (Zhejiang People's Electronics, Zhejiang, China) for 60 seconds or until the mouse exhibited tonic seizures.…”

Section: Methodsmentioning

confidence: 99%

“…5-Hydroxyindoleacetic acid (5-HIAA) is the end product of 5-HT metabolism (11). Our previous research found that the 5-HTP, 5-HT, and 5-HIAA contents and TPH2 activity in the brainstem of DBA/1 mice were significantly decreased compared with those in the brainstem of C57BL/6 mice (12). The intraperitoneal injection of fluoxetine, a selective 5-HT reuptake inhibitor (SSRI), or 5-HTP, the precursor of 5-HT, significantly reduced the incidence of S-IRA in DBA/1 mice (13,14).…”

Section: -Hydroxytryptaminementioning

confidence: 99%

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A High-Tryptophan Diet Reduces Seizure-Induced Respiratory Arrest and Alters the Gut Microbiota in DBA/1 Mice

et al. 2021

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Background and Aims: Central 5-hydroxytryptamine (5-HT) defects are responsible for the occurrence of sudden unexpected death in epilepsy (SUDEP). The DBA/1 mouse is an animal model of SUDEP since the mouse exhibits audiogenic seizure-induced respiratory arrest (S-IRA). The synthesis of central 5-HT is closely related to the gut microbiota. Moreover, emerging studies suggest a possible role for the microbiota in mitigating seizure likelihood. Based on this, we aimed to explore the effect of a high-tryptophan diet (HTD) on SUDEP as well as the synthesis and metabolism of central 5-HT. Furthermore, we investigated the involvement of the gut microbiota in this process.Methods: All DBA/1 mice were subjected to acoustic stimulation to induce seizures. Only those mice that exhibited S-IRA were randomly assigned to the normal diet (ND) group (n = 39) or HTD group (n = 53). After 1 month of dietary intervention, (1) S-IRA rates were evaluated, (2) the concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the plasma and brain were determined by ultra-high-pressure liquid chromatography, and (3) the fecal flora biodiversity and species composition were analyzed by 16S rDNA microbiota profiling.Results: The S-IRA rate in DBA/1 mice was significantly reduced in the HTD group compared with that in the control group. HTD increased the levels of 5-HT and 5-HIAA in both the telencephalon and midbrain. HTD significantly elevated the species richness and diversity of the gut microbiota. Moreover, there was a significant difference in the gut microbiota composition between the two groups, and the intestinal flora was dominated by Proteobacteria and Actinobacteria after HTD.Conclusions: HTD is efficient in lowering S-IRA rates and elevating the central 5-HT level in DBA/1 mice. The gut microbiota was altered after HTD intervention. The significant increase in Proteobacteria and Actinobacteria may be related to the SUDEP-protective effect of HTD. Our findings shed light on a candidate choice of dietary prevention for SUDEP.

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Section: Methodsmentioning

confidence: 99%

Section: -Hydroxytryptaminementioning

confidence: 99%

A High-Tryptophan Diet Reduces Seizure-Induced Respiratory Arrest and Alters the Gut Microbiota in DBA/1 Mice

et al. 2021

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“…PTZ-evoked seizure model, PTZ was administered to non-primed DBA/1 mice of approximately 8 weeks of age. The two models were established just as we described previously [5][6][7][8][9][10][11][12] . TPH2-ChETA to be significantly infected the 5-HT neurons in the DR from our group to modulate the balance between reward and aversion 13 .…”

Section: Animalsmentioning

confidence: 99%

“…S-IRA was evoked by acoustic stimulation or intraperitoneal (IP) administration of PTZ, as we previously described [5][6][7][8][9][10][11][12] . For the acoustic stimulation model, each mouse was placed in a cylindrical plexiglass chamber in a sound-isolated room, and audiogenic seizures (AGSZs)…”

Section: Seizure Induction and Resuscitationmentioning

confidence: 99%

“…The latest advancements of the pathogenesis of SUDEP demonstrated that cardiopulmonary dysfunction plays an important role in the occurrence of SUDEP [1][2][3][4][5] . Our previous findings showed that seizure-induced respiratory arrest (S-IRA) can 3 lead to the occurrence of SUDEP evoked by either acoustic stimulation or pentylenetetrazole (PTZ) in DBA/1 murine models [5][6][7][8][9][10][11][12] , and the incidence of S-IRA by acoustic stimulation or PTZ was significantly reduced by 5-Hydroxytryptophan (5-HTP), a precursor for serotonin synthesis in two models of SUDEP 5 . However, the target of 5-HTP-mediated reduction of S-IRA and SUDEP in the brain remains unclear and still needs to be further explored.…”

Section: Introductionmentioning

confidence: 99%

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Optogenetic activation of the serotonergic neural circuit between the dorsal raphe nucleus and pre-Bötzinger complex contributes to inhibition of seizure-induced respiratory arrest in the DBA/1 mouse SUDEP model

Shen

Lian

et al. 2020

Preprint

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Sudden unexpected death in epilepsy (SUDEP) is the fatal cause leading to the death of epilepsy patients with anti-epileptic drug resistance. However, the underlying mechanism of SUDEP remains to be elusive. Our previous study demonstrated that enhancement of serotonin (5-HT) synthesis by intraperitoneal (IP) injection of 5-hydroxytryptophan in brain significantly reduced the incidence of seizure-induced respiratory arrest (S-IRA) in DBA/1 mice SUDEP models. Given that 5-HT2A receptor (5-HT2AR) acts an important role in mediating respiration system in brain, we hypothesized that 5-HT2AR is of great significance to modulate S-IRA and SUDEP. To test this hypothesis, we examined whether the decreased incidence S-IRA evoked by either acoustic stimulation or PTZ by blocking 5-HT2AR by administration with ketanserin (KET), a selective antagonist of 5HT2AR, in DBA/1 mice SUDEP models to test the role of 5-HT2AR modulating S-IRA. Our results suggested that the decreased incidence of S-IRA by 5-Hydroxytryptophan (5-HTP), a precursor for central nervous system (CNS) serotonin (5-HT) synthesis, was significantly reversed by IP and intracerebroventricularly (ICV) injection of ketanserin in our models. Thus, our data suggested that 5-HT2AR in the brain may be a potential and specific target to prevent SUDEP.

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Dorsal raphe nucleus to pre-Bötzinger complex serotonergic neural circuit is involved in seizure-induced respiratory arrest

Ma¹,

Yu²,

Shen³

et al. 2022

iScience

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Decreased serotonin synthesis is involved in seizure-induced respiratory arrest in DBA/1 mice

Cited by 7 publications

References 24 publications

A High-Tryptophan Diet Reduces Seizure-Induced Respiratory Arrest and Alters the Gut Microbiota in DBA/1 Mice

A High-Tryptophan Diet Reduces Seizure-Induced Respiratory Arrest and Alters the Gut Microbiota in DBA/1 Mice

Optogenetic activation of the serotonergic neural circuit between the dorsal raphe nucleus and pre-Bötzinger complex contributes to inhibition of seizure-induced respiratory arrest in the DBA/1 mouse SUDEP model

Dorsal raphe nucleus to pre-Bötzinger complex serotonergic neural circuit is involved in seizure-induced respiratory arrest

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