Sonographic hypoechogenicity of brainstem raphe nucleus is correlated with electroencephalographic spike frequency in patients with epilepsy

Li, Hanli; Deng, Zi‐Ru; Zhang, Juan; Ding, Chuhan; Shi, Xiaotian; Wang, Long; Chen, Xin; Cao, Li; Wang, Yu

doi:10.1016/j.yebeh.2021.107884

Cited by 2 publications

(2 citation statements)

References 52 publications

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“…In a case-control study of 26 TLE patients, magnetic resonance imaging showed ascending reticular activating system structural and functional connectivity reduction in the TLE patients, and the reduction was associated with the consciousness-impairment frequency and the presence of generalized seizures. Li also reported that brainstem raphe nucleus hypoechogenicity is related to spike frequency in epilepsy patients ( 22 ). Based on previous studies demonstrating the important role of CABP4 in synapse formation and development and that the brainstem has neural loops that maintain and generate epileptic states, we hypothesized that CABP4 (c.464G>A, p.G155D) HE mutations might be caused by abnormalities in the synaptic structure, which may lead to an increased susceptibility to epilepsy.…”

Section: Discussionmentioning

confidence: 94%

CABP4 mutation in mice shows alteration in protein expression level and neuron discharge frequency

Shi,

Liang,

Miao

et al. 2024

Transl Pediatr

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Background The calcium-binding protein 4 ( CABP4 ) gene is a newly identified epilepsy-related gene that might be associated with a rare type of genetic focal epilepsy; that is, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). In vitro , mutant CABP4 causes an increased inward flow voltage of calcium ions and a significant increase in the electrical signal discharge in hippocampus neurons; however, the role of CABP4 in epilepsy has not yet been specifically described, and there is not yet a CABP4 mutant animal model recapitulating the epilepsy phenotype. Methods We introduced a human CABP4 missense mutation into the C57BL/6J mouse genome and generated a knock-in strain carrying a glycine-to-aspartic acid mutation in the gene. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to evaluate the CABP4 expression level. Slice patch-clamp recording was carried out on pyramidal cells of prefrontal cortex layers II and III. Results The CABP4 G155D/+ mutant mice were viable and born at an expected Mendelian ratio. Surprisingly, the heterozygous (HE) mice did not display either an abnormal appearance or an overt seizure phenotype, and there was no statistically significant difference between the HE and wild-type (WT) mice in terms of overall messenger RNA (mRNA) and protein expression. However, the HE mutant mice showed an imbalance in the amount of protein expressed in the brain regions. Additionally, the patch-clamp recordings from the HE mouse layer II/III cortical pyramidal cells revealed an increase in the frequency of micro-excitatory post-synaptic currents (mEPSCs) but no change in the amplitude was observed. Conclusions The findings of this study suggest that the CABP4 p.G155D mutation might be one of the mechanisms underlying seizure onset.

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Section: Discussionmentioning

confidence: 94%

CABP4 mutation in mice shows alteration in protein expression level and neuron discharge frequency

Shi,

Liang,

Miao

et al. 2024

Transl Pediatr

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“…In patients with idiopathic generalized epilepsy with tonic-clonic seizures (IGE-TCS) and depression, patients with hypoechogenic brainstem raphe had significantly higher score of Chinese version Neurological Disorders Depression Inventory for Epilepsy (C-NDDI-E) and Beck Depression Inventory-II (BDI-II), and most patients with IGE-TCS and depression exhibited hypoechogenic brainstem raphe, but few patients with IGE-TCS without depression exhibited hypoechogenic brainstem raphe [77]. Furthermore, epileptic patients with hypoechogenicity in the brainstem raphe had higher epileptic discharge index during sleep period but not during awake period, indicating the modulation of the brainstem raphe in epileptic discharge during the sleep cycle [78]. In TLE patients, the BDI score positively correlated with the binding potential of [ 18 F]MPPF, a 5-HT 1a antagonist, in the raphe nuclei and in the insula contralateral to seizure onset, whereas somatic symptoms positively correlated with the [ 18 F]MPPF binding potential in the ipsilateral hippocampus and bilateral left mid-cingulate gyrus and the inferior dorsolateral frontal cortex [79].…”

Section: The Raphe Nuclei In Comorbidities Of Epilepsymentioning

confidence: 99%

The diverse role of the raphe 5-HTergic systems in epilepsy

et al. 2022

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The raphe nuclei comprise nearly all of 5-hydroxytryptaminergic (5-HTergic) neurons in the brain and are widely acknowledged to participate in the modulation of neural excitability. "Excitability-inhibition imbalance" results in a variety of brain disorders, including epilepsy. Epilepsy is a common neurological disorder characterized by hypersynchronous epileptic seizures accompanied by many psychological, social, cognitive consequences. Current antiepileptic drugs and other therapeutics are not ideal to control epilepsy and its comorbidities. Cumulative evidence suggests that the raphe nuclei and 5-HTergic system play an important role in epilepsy and epilepsy-associated comorbidities. Seizure activities propagate to the raphe nuclei and induce various alterations in different subregions of the raphe nuclei at the cellular and molecular levels. Intervention of the activity of raphe nuclei and raphe 5-HTergic system with pharmacological or genetic approaches, deep brain stimulation or optogenetics produces indeed diverse and even contradictory effects on seizure and epilepsy-associated comorbidities in different epilepsy models. Nevertheless, there are still many open questions left, especially regarding to the relationship between 5-HTergic neural circuit and epilepsy. Understanding of 5-HTergic network in a circuit-and molecule-specific way may not only be therapeutically relevant for increasing the drug specificity and precise treatment in epilepsy, but also provide critical hints for other brain disorders with abnormal neural excitability. In this review we focus on the roles of the raphe 5-HTergic system in epilepsy and epilepsy-associated comorbidities. Besides, further perspectives about the complexity and diversity of the raphe nuclei in epilepsy are also addressed.

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Sonographic hypoechogenicity of brainstem raphe nucleus is correlated with electroencephalographic spike frequency in patients with epilepsy

Cited by 2 publications

References 52 publications

CABP4 mutation in mice shows alteration in protein expression level and neuron discharge frequency

CABP4 mutation in mice shows alteration in protein expression level and neuron discharge frequency

The diverse role of the raphe 5-HTergic systems in epilepsy

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