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ORIGINAL RESEARCH article

Front. Neurol.
Sec. Pediatric Neurology
Volume 15 - 2024 | doi: 10.3389/fneur.2024.1500737

Decreased Neuronal Excitability in Hypertriglyceridemia Hamsters with Acute Seizures

Provisionally accepted
Qiuyue Shen Qiuyue Shen 1,2Nana Liu Nana Liu 1,2Yuwu Jiang Yuwu Jiang 1,2Lili Liu Lili Liu 1,2*Xinlin Hou Xinlin Hou 1,2*
  • 1 First Hospital, Peking University, Beijing, China
  • 2 Department of Pediatrics, First Hospital, Peking University, Beijing, Beijing Municipality, China

The final, formatted version of the article will be published soon.

    Introduction: Neonatal seizures are the most common clinical manifestation of neurological dysfunction in newborns, with an incidence ranging from 1-5‰. However, the therapeutic efficacy of current pharmacological treatments remains suboptimal. This study aims to utilize genetically modified hamsters with hypertriglyceridaemia (HTG) to investigate the effects of elevated triglycerides on neuronal excitability and to elucidate the underlying mechanisms. The ultimate goal is to identify novel therapeutic targets for the treatment of neonatal seizures.Methods: Acute seizure models were established both in vivo and ex vivo using wild-type and Apolipoprotein C2 knockout (Apoc2 -/-) hamsters. The frequency of tonic-clonic seizures was recorded.Excitatory postsynaptic potentials (EPSPs) and evoked action potentials (eAPs) of pyramidal neurons in the frontal cortex were measured. Fatty acid metabolomic analysis was conducted on microdialysate from the frontal cortex tissue post-seizure, and mRNA expression changes were also assessed.Results: Apoc2 -/-hamsters exhibited a reduced frequency of tonic-clonic seizures and diminished EPSP and eAP in comparison to wild-type hamsters. Following seizure induction, free palmitic acid levels in the frontal cortex dialysate significantly decreased, while the expression of palmitoyl acyltransferase 14 (ZDHHC14) in the frontal cortex tissue was higher in Apoc2 -/-hamsters than in wild-type hamsters. Additionally, the amplitude of transient outward potassium currents (IA) in cortical neurons of Apoc2 -/-hamsters was observed to be elevated compared to wild-type hamsters.Hypertriglyceridemic Apoc2 -/-hamsters exhibited reduced seizure frequency and decreased cortical neuron excitability. The upregulation of ZDHHC14, leading to increased IA, may be a crucial mechanism underlying the observed seizure protection.

    Keywords: seizure, Hypertriglyceridemia, ZDHHC14, Transient outward K + currents, Palmitoylation modification

    Received: 23 Sep 2024; Accepted: 04 Dec 2024.

    Copyright: © 2024 Shen, Liu, Jiang, Liu and Hou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Lili Liu, Department of Pediatrics, First Hospital, Peking University, Beijing, 100006, Beijing Municipality, China
    Xinlin Hou, Department of Pediatrics, First Hospital, Peking University, Beijing, 100006, Beijing Municipality, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.