Regeneration of Neurotransmission Transcriptome in a Model of Epileptic Encephalopathy after Antiinflammatory Treatment

Authors

Dumitru Iacobas, New York Medical CollegeFollow
Libor Velisek, New York Medical CollegeFollow

Author ORCID Identifier

0000-0001-9700-6537

DOI

10.4103/1673-5374.238607

Journal Title

Neural Regeneration Research

First Page

1715

Last Page

1718

Document Type

Article

Publication Date

10-1-2018

Department

Pathology, Microbiology and Immunology

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 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.

Recommended Citation

Iacobas, D., & Velisek, L. (2018). Regeneration of Neurotransmission Transcriptome in a Model of Epileptic Encephalopathy after Antiinflammatory Treatment. Neural Regeneration Research, 13 (10), 1715-1718. https://doi.org/10.4103/1673-5374.238607

Publisher's Statement

Originally published in Neural Regeneration Research, 13(10), 1715-1718. The original material can be found here.

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This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.