ACTH and PMX53 recover synaptic transcriptome alterations in a rat model of infantile spasms

Abstract We profiled the gene expression in the hypothalamic arcuate nuclei (ARC) of 20 male and 20 female rats to determine the infantile spasms (IS) related transcriptomic alteration of neurotransmission and recovery following two treatments. Rats were prenatally exposed to betamethasone or saline...

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Autores principales:	Dumitru A. Iacobaş, Tamar Chachua, Sanda Iacobaş, Melissa J. Benson, Karin Borges, Jana Velíšková, Libor Velíšek
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c1c038ab3d384dc3a8d178380bb0ec24
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spelling	oai:doaj.org-article:c1c038ab3d384dc3a8d178380bb0ec242021-12-02T15:08:14ZACTH and PMX53 recover synaptic transcriptome alterations in a rat model of infantile spasms10.1038/s41598-018-24013-x2045-2322https://doaj.org/article/c1c038ab3d384dc3a8d178380bb0ec242018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24013-xhttps://doaj.org/toc/2045-2322Abstract We profiled the gene expression in the hypothalamic arcuate nuclei (ARC) of 20 male and 20 female rats to determine the infantile spasms (IS) related transcriptomic alteration of neurotransmission and recovery following two treatments. Rats were prenatally exposed to betamethasone or saline followed by repeated postnatal subjection to NMDA-triggered IS. Rats with spasms were treated with ACTH, PMX53 or saline. Since ACTH, the first line treatment for IS, has inconsistent efficacy and potential harsh side effects, PMX53, a potent complement C5ar1 antagonist, was suggested as a therapeutic alternative given its effects in other epilepsy models. Novel measures that consider all genes and are not affected by arbitrary cut-offs were used, in addition to standard statistical tests, to quantify regulation and recovery of glutamatergic, GABAergic, cholinergic, dopaminergic and serotonergic pathways. Although IS alters expression of ~30% of the ARC genes in both sexes the transcriptomic effects are 3× more severe in males than their female counterparts, as indicated by the Weighted Pathway Regulation measure. Both treatments significantly restored the ARC neurotransmission transcriptome to the non-IS condition with PMX53 performing slightly better, as measured by the Pathway Restoration Efficiency, suggesting these treatments may reduce autistic traits often associated with IS.Dumitru A. IacobaşTamar ChachuaSanda IacobaşMelissa J. BensonKarin BorgesJana VelíškováLibor VelíšekNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dumitru A. Iacobaş Tamar Chachua Sanda Iacobaş Melissa J. Benson Karin Borges Jana Velíšková Libor Velíšek ACTH and PMX53 recover synaptic transcriptome alterations in a rat model of infantile spasms
description	Abstract We profiled the gene expression in the hypothalamic arcuate nuclei (ARC) of 20 male and 20 female rats to determine the infantile spasms (IS) related transcriptomic alteration of neurotransmission and recovery following two treatments. Rats were prenatally exposed to betamethasone or saline followed by repeated postnatal subjection to NMDA-triggered IS. Rats with spasms were treated with ACTH, PMX53 or saline. Since ACTH, the first line treatment for IS, has inconsistent efficacy and potential harsh side effects, PMX53, a potent complement C5ar1 antagonist, was suggested as a therapeutic alternative given its effects in other epilepsy models. Novel measures that consider all genes and are not affected by arbitrary cut-offs were used, in addition to standard statistical tests, to quantify regulation and recovery of glutamatergic, GABAergic, cholinergic, dopaminergic and serotonergic pathways. Although IS alters expression of ~30% of the ARC genes in both sexes the transcriptomic effects are 3× more severe in males than their female counterparts, as indicated by the Weighted Pathway Regulation measure. Both treatments significantly restored the ARC neurotransmission transcriptome to the non-IS condition with PMX53 performing slightly better, as measured by the Pathway Restoration Efficiency, suggesting these treatments may reduce autistic traits often associated with IS.
format	article
author	Dumitru A. Iacobaş Tamar Chachua Sanda Iacobaş Melissa J. Benson Karin Borges Jana Velíšková Libor Velíšek
author_facet	Dumitru A. Iacobaş Tamar Chachua Sanda Iacobaş Melissa J. Benson Karin Borges Jana Velíšková Libor Velíšek
author_sort	Dumitru A. Iacobaş
title	ACTH and PMX53 recover synaptic transcriptome alterations in a rat model of infantile spasms
title_short	ACTH and PMX53 recover synaptic transcriptome alterations in a rat model of infantile spasms
title_full	ACTH and PMX53 recover synaptic transcriptome alterations in a rat model of infantile spasms
title_fullStr	ACTH and PMX53 recover synaptic transcriptome alterations in a rat model of infantile spasms
title_full_unstemmed	ACTH and PMX53 recover synaptic transcriptome alterations in a rat model of infantile spasms
title_sort	acth and pmx53 recover synaptic transcriptome alterations in a rat model of infantile spasms
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/c1c038ab3d384dc3a8d178380bb0ec24
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ACTH and PMX53 recover synaptic transcriptome alterations in a rat model of infantile spasms

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