中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (9): 1867-1868.doi: 10.4103/1673-5374.390967

• 观点:脑损伤修复保护与再生 • 上一篇    下一篇

新的复杂生理学发现发展了Dravet综合征的假设机制

  

  • 出版日期:2024-09-15 发布日期:2024-01-25

New complex physiological findings evolve hypothesized mechanisms of Dravet syndrome

MacKenzie A. Howard*   

  1. Department of Neurology, Dell Medical School, Austin, TX, USA
    Center for Learning and Memory and Department of Neuroscience, University of Texas at Austin, Austin, TX, USA
  • Online:2024-09-15 Published:2024-01-25
  • Contact: MacKenzie A. Howard, PhD, mackenziehoward@austin.utexas.edu.
  • Supported by:
    This work was supported by Dravet Syndrome Foundation, NIH/NINDS R01-NS112500.

摘要: https://orcid.org/0000-0003-2832-6873 (MacKenzie A. Howard)

Abstract: Developmental and epileptic encephalopathies (DEEs) are neurological disorders generally involving medically intractable seizures and a diverse array of comorbid neuropsychiatric delays and deficits that may severely affect cognition, mood, sleep, social behavior, movement control, learning, and/or memory. Dravet syndrome (DS), also known as Severe Myoclonic Epilepsy of Infancy, is a rare disease but one of the more common DEEs, afflicting children in infancy and causing severe lifelong struggles and high risk of early mortality (Villas et al., 2017). Most people with DS have a deleterious variant to one copy of the SCN1A gene, which encodes the voltage-gated sodium channel Nav1.1. Variants of SCN1B, HCN1, and other genes have also been identified as potentially causative in diagnosed cases of DS. Animal models across phyla with changes to the expression of Scn1a or its ortholog present with seizures, neurological deficits, and early mortality analogous to DS. Early animal model work provided a wealth of knowledge about the role of Nav1.1 in neural excitability and dysfunction and brought about the hypothesis that GABAergic interneuron hypoexcitability was the underlying cause of DS. Here we provide a brief review of some recent studies that broaden the interneuron hypothesis, revealing cell phenotypes and circuit interactions that are subtle, complex, and at times counterintuitive, all while deepening our understanding of the intricate nature of neural processing and the mechanisms of neurological disease.