Regeneration of neurotransmission transcriptome in a model of epileptic encephalopathy after antiinflammatory treatment.
Regeneration of neurotransmission transcriptome in a model of epileptic encephalopathy after antiinflammatory treatment.
复制标题
DOI：
10.4103/1673-5374.238607
复制
发表时间：
2018-10
影响因子：
6.1
通讯作者：
Velíšek L
中科院分区：
文献类型：
--
作者：
Iacobas DA;Velíšek L
炎症是婴儿痉挛（is）的一个确定的致病因素，is是一种婴儿治疗抵抗性癫痫综合征。我们研究了is相关的大鼠下丘脑弓状核神经传递的转录组改变，它们是如何通过抗炎治疗来纠正的，以及是否存在性别差异。对产前暴露于倍他米松的幼鼠，在抗炎治疗（促肾上腺皮质激素（ACTH）或PMX53）后反复腹腔注射n -甲基- d -天冬氨酸或生理盐水引起IS。我们发现ACTH和PMX53治疗导致IS改变的所有类型突触传递的基因组结构的实质性恢复。虽然ACTH是IS的一线治疗方法，但PMX53（补体C5a受体拮抗剂）在恢复正常转录组方面的效率更高，这是意料之外的。除了儿童癫痫，PMX53对神经传递基因组结构的恢复也给自闭症谱系障碍带来了希望，自闭症谱系障碍与IS有很高的合并症。我们的研究结果显示，在is相关的转录组改变（男性更受影响）和PMX53抗炎治疗的效率（男性更好）方面存在显著的性别差异。我们的数据进一步表明，纠正炎症转录组改变的抗炎治疗可能成为难治性癫痫的成功治疗方法。
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.
登录
查看更多内容
影响因子：
5.6
作者：
Aronica E;Bauer S;Bozzi Y;Caleo M;Dingledine R;Gorter JA;Henshall DC;Kaufer D;Koh S;Löscher W;Louboutin JP;Mishto M;Norwood BA;Palma E;Poulter MO;Terrone G;Vezzani A;Kaminski RM
通讯作者：
Kaminski RM
影响因子：
5.8
作者：
Iacobas, Dumitru A.;Iacobas, Sanda;Spray, David C.
通讯作者：
Spray, David C.
影响因子：
3.3
作者：
Das, A.;Wallace, G. C.;Holmes, C.;McDowell, M. L.;Smith, J. A.;Marshall, J. D.;Bonilha, L.;Edwards, J. C.;Glazier, S. S.;Ray, S. K.;Banik, N. L.
通讯作者：
Banik, N. L.
影响因子：
3.7
作者：
Laurén HB;Lopez-Picon FR;Brandt AM;Rios-Rojas CJ;Holopainen IE
通讯作者：
Holopainen IE
影响因子：
5.6
作者：
Yum MS;Chachua T;Velíšková J;Velíšek L
通讯作者：
Velíšek L