中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (10): 1715-1718.doi: 10.4103/1673-5374.238607

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

抗炎治疗后癫痫性脑病模型神经传递转录组的再生

  

  • 收稿日期:2018-07-05 出版日期:2018-10-15 发布日期:2018-10-15

Regeneration of neurotransmission transcriptome in a model of epileptic encephalopathy after antiinflammatory treatment

Dumitru A. Iacobaş1, 2, Libor Velíšek3, 4, 5   

  1. 1 Center for Computational Systems Biology, Prairie View AM University, Prairie View, TX, USA
    2 D.P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, NY, USA
    3 Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY, USA
    4 Department of Neurology, New York Medical College, Valhalla, NY, USA
    5 Department of Pediatrics, New York Medical College, Valhalla, NY, USA
  • Received:2018-07-05 Online:2018-10-15 Published:2018-10-15
  • Contact: Dumitru A. Iacoba?, PhD,daiacobas@pvamu.edu.
  • Supported by:

    This study was supported by Citizens United for Research in Epilepsy (CURE) Infantile Spasms Research Initiative (to LV, and DAI) and NIH grant NS-072966 (to LV).

摘要:

orcid:0000-0001-9700-6537(Dumitru A. Iacoba?

Abstract:

Inflammation is an established etiopathogenesis factor of infantile spasms (IS), a therapy-resistant epileptic syndrome of infancy. We investigated the IS-associated transcriptomic alterations of neurotransmission in rat hypothalamic arcuate nucleus, how they are corrected by antiinflamatory treatments and whether there are sex differences. IS was triggered by repeated intraperitoneal administration of N-methyl-D-aspartic acid (NMDA) following anti-inflammatory treatment (adreno-cortico-tropic-hormone (ACTH) or PMX53) or normal saline vehicle to prenatally exposed to betamethasone young rats. We found that treatments with both ACTH and PMX53 resulted in substantial recovery of the genomic fabrics of all types of synaptic transmission altered by IS. While ACTH represents the first line of treatment for IS, the even higher efficiency of PMX53 (an antagonist of the complement C5a receptor) in restoring the normal transcriptome was not expected. In addition to the childhood epilepsy, the recovery of the neurotransmission genomic fabrics by PMX53 also gives hope for the autism spectrum disorders that share a high comorbidity with IS. Our results revealed significant sex dichotomy in both IS-associated transcriptomic alterations (males more affected) and in the efficiency of PMX53 anti-inflammatory treatment (better for males). Our data further suggest that anti-inflammatory treatments correcting alterations in the inflammatory transcriptome may become successful therapies for refractory epilepsies.

Key words: adreno-cortico-tropic-hormone, autism, cholinergic transmission, hypothalamus, infantile spasms, microarrays, PMX53, sex differences