Estrogen Protects Neurotransmission Transcriptome During Status Epilepticus

Women with epilepsy commonly have premature onset of menopause. The decrease in estrogen levels is associated with increased occurrence of neurodegenerative processes and cognitive decline. Previously, we found that estradiol (E2) replacement in ovariectomized (OVX) female rats significantly reduced the seizure-related damage in the sensitive hilar region of hippocampal dentate gyrus (DG). However, the complex mechanisms by which E2 empowers the genomic fabrics of neurotransmission to resist damaging effects of status epilepticus (SE) are still unclear. We determined the protective effects of the estradiol replacement against kainic acid-induced SE-associated transcriptomic alterations in the DG of OVX rats. Without E2 replacement, SE altered expression of 44% of the DG genes. SE affected all major functional pathways, including apoptosis (61%), Alzheimer's disease (47%), cell cycle (59%), long-term potentiation (62%), and depression (55%), as well as synaptic vesicle cycle (62%), glutamatergic (53%), GABAergic (49%), cholinergic (52%), dopaminergic (55%), and serotonergic (49%) neurotransmission. However, in rats with E2 replacement the percentage of significantly affected genes after SE was reduced to the average 11% (from 8% for apoptosis to 32% for GABAergic synapse). Interestingly, while SE down-regulated most of the synaptic receptor genes in oil-injected females it had little effect on these receptors after E2-replacement. Our novel Pathway Protection analysis indicated that the E2-replacement prevented SE-related damage from 50% for GABA to 75% for dopaminergic transmission. The 15% synergistic expression between genes involved in estrogen signaling (ESG) and neurotransmission explains why low E2 levels result in down-regulation of neurotransmission. Interestingly, in animals with E2-replacement, SE switched 131 synergistically expressed ESG-neurotransmission gene pairs into antagonistically expressed gene pairs. Thus, the ESG pathway acts like a buffer against SE-induced alteration of neurotransmission that may contribute to the E2-mediated maintenance of brain function after the SE injury in postmenopausal women. We also show that the long-term potentiation is lost in OVX rats following SE but not in those with E2 replacement. The electrophysiological findings in OVX female rats with SE are corroborated by the high percentage of long-term potentiation regulated genes (62%) in oil-injected while only 13% of genes were regulated following SE in E2-replaced rats. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Dumitru A. Iacobas [verfasserIn] Sanda Iacobas [verfasserIn] Nino Nebieridze [verfasserIn] Libor Velíšek [verfasserIn] Jana Velíšková [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	beta-estradiol cholinergic synapse dentate gyrus dopaminergic synapse GABAergic synapse glutamatergic synapse

Übergeordnetes Werk:	In: Frontiers in Neuroscience - Frontiers Media S.A., 2008, 12(2018)
Übergeordnetes Werk:	volume:12 ; year:2018

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fnins.2018.00332

Katalog-ID:	DOAJ071912908

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allfields	10.3389/fnins.2018.00332 doi (DE-627)DOAJ071912908 (DE-599)DOAJ9ba7cc7b79d4490f8cd0a694de2b26b8 DE-627 ger DE-627 rakwb eng RC321-571 Dumitru A. Iacobas verfasserin aut Estrogen Protects Neurotransmission Transcriptome During Status Epilepticus 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Women with epilepsy commonly have premature onset of menopause. The decrease in estrogen levels is associated with increased occurrence of neurodegenerative processes and cognitive decline. Previously, we found that estradiol (E2) replacement in ovariectomized (OVX) female rats significantly reduced the seizure-related damage in the sensitive hilar region of hippocampal dentate gyrus (DG). However, the complex mechanisms by which E2 empowers the genomic fabrics of neurotransmission to resist damaging effects of status epilepticus (SE) are still unclear. We determined the protective effects of the estradiol replacement against kainic acid-induced SE-associated transcriptomic alterations in the DG of OVX rats. Without E2 replacement, SE altered expression of 44% of the DG genes. SE affected all major functional pathways, including apoptosis (61%), Alzheimer's disease (47%), cell cycle (59%), long-term potentiation (62%), and depression (55%), as well as synaptic vesicle cycle (62%), glutamatergic (53%), GABAergic (49%), cholinergic (52%), dopaminergic (55%), and serotonergic (49%) neurotransmission. However, in rats with E2 replacement the percentage of significantly affected genes after SE was reduced to the average 11% (from 8% for apoptosis to 32% for GABAergic synapse). Interestingly, while SE down-regulated most of the synaptic receptor genes in oil-injected females it had little effect on these receptors after E2-replacement. Our novel Pathway Protection analysis indicated that the E2-replacement prevented SE-related damage from 50% for GABA to 75% for dopaminergic transmission. The 15% synergistic expression between genes involved in estrogen signaling (ESG) and neurotransmission explains why low E2 levels result in down-regulation of neurotransmission. Interestingly, in animals with E2-replacement, SE switched 131 synergistically expressed ESG-neurotransmission gene pairs into antagonistically expressed gene pairs. Thus, the ESG pathway acts like a buffer against SE-induced alteration of neurotransmission that may contribute to the E2-mediated maintenance of brain function after the SE injury in postmenopausal women. We also show that the long-term potentiation is lost in OVX rats following SE but not in those with E2 replacement. The electrophysiological findings in OVX female rats with SE are corroborated by the high percentage of long-term potentiation regulated genes (62%) in oil-injected while only 13% of genes were regulated following SE in E2-replaced rats. beta-estradiol cholinergic synapse dentate gyrus dopaminergic synapse GABAergic synapse glutamatergic synapse Neurosciences. Biological psychiatry. Neuropsychiatry Dumitru A. Iacobas verfasserin aut Sanda Iacobas verfasserin aut Sanda Iacobas verfasserin aut Nino Nebieridze verfasserin aut Libor Velíšek verfasserin aut Libor Velíšek verfasserin aut Libor Velíšek verfasserin aut Jana Velíšková verfasserin aut Jana Velíšková verfasserin aut Jana Velíšková verfasserin aut In Frontiers in Neuroscience Frontiers Media S.A., 2008 12(2018) (DE-627)55908109X (DE-600)2411902-7 1662453X nnns volume:12 year:2018 https://doi.org/10.3389/fnins.2018.00332 kostenfrei https://doaj.org/article/9ba7cc7b79d4490f8cd0a694de2b26b8 kostenfrei https://www.frontiersin.org/article/10.3389/fnins.2018.00332/full kostenfrei https://doaj.org/toc/1662-453X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2018
spelling	10.3389/fnins.2018.00332 doi (DE-627)DOAJ071912908 (DE-599)DOAJ9ba7cc7b79d4490f8cd0a694de2b26b8 DE-627 ger DE-627 rakwb eng RC321-571 Dumitru A. Iacobas verfasserin aut Estrogen Protects Neurotransmission Transcriptome During Status Epilepticus 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Women with epilepsy commonly have premature onset of menopause. The decrease in estrogen levels is associated with increased occurrence of neurodegenerative processes and cognitive decline. Previously, we found that estradiol (E2) replacement in ovariectomized (OVX) female rats significantly reduced the seizure-related damage in the sensitive hilar region of hippocampal dentate gyrus (DG). However, the complex mechanisms by which E2 empowers the genomic fabrics of neurotransmission to resist damaging effects of status epilepticus (SE) are still unclear. We determined the protective effects of the estradiol replacement against kainic acid-induced SE-associated transcriptomic alterations in the DG of OVX rats. Without E2 replacement, SE altered expression of 44% of the DG genes. SE affected all major functional pathways, including apoptosis (61%), Alzheimer's disease (47%), cell cycle (59%), long-term potentiation (62%), and depression (55%), as well as synaptic vesicle cycle (62%), glutamatergic (53%), GABAergic (49%), cholinergic (52%), dopaminergic (55%), and serotonergic (49%) neurotransmission. However, in rats with E2 replacement the percentage of significantly affected genes after SE was reduced to the average 11% (from 8% for apoptosis to 32% for GABAergic synapse). Interestingly, while SE down-regulated most of the synaptic receptor genes in oil-injected females it had little effect on these receptors after E2-replacement. Our novel Pathway Protection analysis indicated that the E2-replacement prevented SE-related damage from 50% for GABA to 75% for dopaminergic transmission. The 15% synergistic expression between genes involved in estrogen signaling (ESG) and neurotransmission explains why low E2 levels result in down-regulation of neurotransmission. Interestingly, in animals with E2-replacement, SE switched 131 synergistically expressed ESG-neurotransmission gene pairs into antagonistically expressed gene pairs. Thus, the ESG pathway acts like a buffer against SE-induced alteration of neurotransmission that may contribute to the E2-mediated maintenance of brain function after the SE injury in postmenopausal women. We also show that the long-term potentiation is lost in OVX rats following SE but not in those with E2 replacement. The electrophysiological findings in OVX female rats with SE are corroborated by the high percentage of long-term potentiation regulated genes (62%) in oil-injected while only 13% of genes were regulated following SE in E2-replaced rats. beta-estradiol cholinergic synapse dentate gyrus dopaminergic synapse GABAergic synapse glutamatergic synapse Neurosciences. Biological psychiatry. Neuropsychiatry Dumitru A. Iacobas verfasserin aut Sanda Iacobas verfasserin aut Sanda Iacobas verfasserin aut Nino Nebieridze verfasserin aut Libor Velíšek verfasserin aut Libor Velíšek verfasserin aut Libor Velíšek verfasserin aut Jana Velíšková verfasserin aut Jana Velíšková verfasserin aut Jana Velíšková verfasserin aut In Frontiers in Neuroscience Frontiers Media S.A., 2008 12(2018) (DE-627)55908109X (DE-600)2411902-7 1662453X nnns volume:12 year:2018 https://doi.org/10.3389/fnins.2018.00332 kostenfrei https://doaj.org/article/9ba7cc7b79d4490f8cd0a694de2b26b8 kostenfrei https://www.frontiersin.org/article/10.3389/fnins.2018.00332/full kostenfrei https://doaj.org/toc/1662-453X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2018
allfields_unstemmed	10.3389/fnins.2018.00332 doi (DE-627)DOAJ071912908 (DE-599)DOAJ9ba7cc7b79d4490f8cd0a694de2b26b8 DE-627 ger DE-627 rakwb eng RC321-571 Dumitru A. Iacobas verfasserin aut Estrogen Protects Neurotransmission Transcriptome During Status Epilepticus 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Women with epilepsy commonly have premature onset of menopause. The decrease in estrogen levels is associated with increased occurrence of neurodegenerative processes and cognitive decline. Previously, we found that estradiol (E2) replacement in ovariectomized (OVX) female rats significantly reduced the seizure-related damage in the sensitive hilar region of hippocampal dentate gyrus (DG). However, the complex mechanisms by which E2 empowers the genomic fabrics of neurotransmission to resist damaging effects of status epilepticus (SE) are still unclear. We determined the protective effects of the estradiol replacement against kainic acid-induced SE-associated transcriptomic alterations in the DG of OVX rats. Without E2 replacement, SE altered expression of 44% of the DG genes. SE affected all major functional pathways, including apoptosis (61%), Alzheimer's disease (47%), cell cycle (59%), long-term potentiation (62%), and depression (55%), as well as synaptic vesicle cycle (62%), glutamatergic (53%), GABAergic (49%), cholinergic (52%), dopaminergic (55%), and serotonergic (49%) neurotransmission. However, in rats with E2 replacement the percentage of significantly affected genes after SE was reduced to the average 11% (from 8% for apoptosis to 32% for GABAergic synapse). Interestingly, while SE down-regulated most of the synaptic receptor genes in oil-injected females it had little effect on these receptors after E2-replacement. Our novel Pathway Protection analysis indicated that the E2-replacement prevented SE-related damage from 50% for GABA to 75% for dopaminergic transmission. The 15% synergistic expression between genes involved in estrogen signaling (ESG) and neurotransmission explains why low E2 levels result in down-regulation of neurotransmission. Interestingly, in animals with E2-replacement, SE switched 131 synergistically expressed ESG-neurotransmission gene pairs into antagonistically expressed gene pairs. Thus, the ESG pathway acts like a buffer against SE-induced alteration of neurotransmission that may contribute to the E2-mediated maintenance of brain function after the SE injury in postmenopausal women. We also show that the long-term potentiation is lost in OVX rats following SE but not in those with E2 replacement. The electrophysiological findings in OVX female rats with SE are corroborated by the high percentage of long-term potentiation regulated genes (62%) in oil-injected while only 13% of genes were regulated following SE in E2-replaced rats. beta-estradiol cholinergic synapse dentate gyrus dopaminergic synapse GABAergic synapse glutamatergic synapse Neurosciences. Biological psychiatry. Neuropsychiatry Dumitru A. Iacobas verfasserin aut Sanda Iacobas verfasserin aut Sanda Iacobas verfasserin aut Nino Nebieridze verfasserin aut Libor Velíšek verfasserin aut Libor Velíšek verfasserin aut Libor Velíšek verfasserin aut Jana Velíšková verfasserin aut Jana Velíšková verfasserin aut Jana Velíšková verfasserin aut In Frontiers in Neuroscience Frontiers Media S.A., 2008 12(2018) (DE-627)55908109X (DE-600)2411902-7 1662453X nnns volume:12 year:2018 https://doi.org/10.3389/fnins.2018.00332 kostenfrei https://doaj.org/article/9ba7cc7b79d4490f8cd0a694de2b26b8 kostenfrei https://www.frontiersin.org/article/10.3389/fnins.2018.00332/full kostenfrei https://doaj.org/toc/1662-453X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2018
allfieldsGer	10.3389/fnins.2018.00332 doi (DE-627)DOAJ071912908 (DE-599)DOAJ9ba7cc7b79d4490f8cd0a694de2b26b8 DE-627 ger DE-627 rakwb eng RC321-571 Dumitru A. Iacobas verfasserin aut Estrogen Protects Neurotransmission Transcriptome During Status Epilepticus 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Women with epilepsy commonly have premature onset of menopause. The decrease in estrogen levels is associated with increased occurrence of neurodegenerative processes and cognitive decline. Previously, we found that estradiol (E2) replacement in ovariectomized (OVX) female rats significantly reduced the seizure-related damage in the sensitive hilar region of hippocampal dentate gyrus (DG). However, the complex mechanisms by which E2 empowers the genomic fabrics of neurotransmission to resist damaging effects of status epilepticus (SE) are still unclear. We determined the protective effects of the estradiol replacement against kainic acid-induced SE-associated transcriptomic alterations in the DG of OVX rats. Without E2 replacement, SE altered expression of 44% of the DG genes. SE affected all major functional pathways, including apoptosis (61%), Alzheimer's disease (47%), cell cycle (59%), long-term potentiation (62%), and depression (55%), as well as synaptic vesicle cycle (62%), glutamatergic (53%), GABAergic (49%), cholinergic (52%), dopaminergic (55%), and serotonergic (49%) neurotransmission. However, in rats with E2 replacement the percentage of significantly affected genes after SE was reduced to the average 11% (from 8% for apoptosis to 32% for GABAergic synapse). Interestingly, while SE down-regulated most of the synaptic receptor genes in oil-injected females it had little effect on these receptors after E2-replacement. Our novel Pathway Protection analysis indicated that the E2-replacement prevented SE-related damage from 50% for GABA to 75% for dopaminergic transmission. The 15% synergistic expression between genes involved in estrogen signaling (ESG) and neurotransmission explains why low E2 levels result in down-regulation of neurotransmission. Interestingly, in animals with E2-replacement, SE switched 131 synergistically expressed ESG-neurotransmission gene pairs into antagonistically expressed gene pairs. Thus, the ESG pathway acts like a buffer against SE-induced alteration of neurotransmission that may contribute to the E2-mediated maintenance of brain function after the SE injury in postmenopausal women. We also show that the long-term potentiation is lost in OVX rats following SE but not in those with E2 replacement. The electrophysiological findings in OVX female rats with SE are corroborated by the high percentage of long-term potentiation regulated genes (62%) in oil-injected while only 13% of genes were regulated following SE in E2-replaced rats. beta-estradiol cholinergic synapse dentate gyrus dopaminergic synapse GABAergic synapse glutamatergic synapse Neurosciences. Biological psychiatry. Neuropsychiatry Dumitru A. Iacobas verfasserin aut Sanda Iacobas verfasserin aut Sanda Iacobas verfasserin aut Nino Nebieridze verfasserin aut Libor Velíšek verfasserin aut Libor Velíšek verfasserin aut Libor Velíšek verfasserin aut Jana Velíšková verfasserin aut Jana Velíšková verfasserin aut Jana Velíšková verfasserin aut In Frontiers in Neuroscience Frontiers Media S.A., 2008 12(2018) (DE-627)55908109X (DE-600)2411902-7 1662453X nnns volume:12 year:2018 https://doi.org/10.3389/fnins.2018.00332 kostenfrei https://doaj.org/article/9ba7cc7b79d4490f8cd0a694de2b26b8 kostenfrei https://www.frontiersin.org/article/10.3389/fnins.2018.00332/full kostenfrei https://doaj.org/toc/1662-453X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2018
allfieldsSound	10.3389/fnins.2018.00332 doi (DE-627)DOAJ071912908 (DE-599)DOAJ9ba7cc7b79d4490f8cd0a694de2b26b8 DE-627 ger DE-627 rakwb eng RC321-571 Dumitru A. Iacobas verfasserin aut Estrogen Protects Neurotransmission Transcriptome During Status Epilepticus 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Women with epilepsy commonly have premature onset of menopause. The decrease in estrogen levels is associated with increased occurrence of neurodegenerative processes and cognitive decline. Previously, we found that estradiol (E2) replacement in ovariectomized (OVX) female rats significantly reduced the seizure-related damage in the sensitive hilar region of hippocampal dentate gyrus (DG). However, the complex mechanisms by which E2 empowers the genomic fabrics of neurotransmission to resist damaging effects of status epilepticus (SE) are still unclear. We determined the protective effects of the estradiol replacement against kainic acid-induced SE-associated transcriptomic alterations in the DG of OVX rats. Without E2 replacement, SE altered expression of 44% of the DG genes. SE affected all major functional pathways, including apoptosis (61%), Alzheimer's disease (47%), cell cycle (59%), long-term potentiation (62%), and depression (55%), as well as synaptic vesicle cycle (62%), glutamatergic (53%), GABAergic (49%), cholinergic (52%), dopaminergic (55%), and serotonergic (49%) neurotransmission. However, in rats with E2 replacement the percentage of significantly affected genes after SE was reduced to the average 11% (from 8% for apoptosis to 32% for GABAergic synapse). Interestingly, while SE down-regulated most of the synaptic receptor genes in oil-injected females it had little effect on these receptors after E2-replacement. Our novel Pathway Protection analysis indicated that the E2-replacement prevented SE-related damage from 50% for GABA to 75% for dopaminergic transmission. The 15% synergistic expression between genes involved in estrogen signaling (ESG) and neurotransmission explains why low E2 levels result in down-regulation of neurotransmission. Interestingly, in animals with E2-replacement, SE switched 131 synergistically expressed ESG-neurotransmission gene pairs into antagonistically expressed gene pairs. Thus, the ESG pathway acts like a buffer against SE-induced alteration of neurotransmission that may contribute to the E2-mediated maintenance of brain function after the SE injury in postmenopausal women. We also show that the long-term potentiation is lost in OVX rats following SE but not in those with E2 replacement. The electrophysiological findings in OVX female rats with SE are corroborated by the high percentage of long-term potentiation regulated genes (62%) in oil-injected while only 13% of genes were regulated following SE in E2-replaced rats. beta-estradiol cholinergic synapse dentate gyrus dopaminergic synapse GABAergic synapse glutamatergic synapse Neurosciences. Biological psychiatry. Neuropsychiatry Dumitru A. Iacobas verfasserin aut Sanda Iacobas verfasserin aut Sanda Iacobas verfasserin aut Nino Nebieridze verfasserin aut Libor Velíšek verfasserin aut Libor Velíšek verfasserin aut Libor Velíšek verfasserin aut Jana Velíšková verfasserin aut Jana Velíšková verfasserin aut Jana Velíšková verfasserin aut In Frontiers in Neuroscience Frontiers Media S.A., 2008 12(2018) (DE-627)55908109X (DE-600)2411902-7 1662453X nnns volume:12 year:2018 https://doi.org/10.3389/fnins.2018.00332 kostenfrei https://doaj.org/article/9ba7cc7b79d4490f8cd0a694de2b26b8 kostenfrei https://www.frontiersin.org/article/10.3389/fnins.2018.00332/full kostenfrei https://doaj.org/toc/1662-453X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2018
language	English
source	In Frontiers in Neuroscience 12(2018) volume:12 year:2018
sourceStr	In Frontiers in Neuroscience 12(2018) volume:12 year:2018
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	beta-estradiol cholinergic synapse dentate gyrus dopaminergic synapse GABAergic synapse glutamatergic synapse Neurosciences. Biological psychiatry. Neuropsychiatry
isfreeaccess_bool	true
container_title	Frontiers in Neuroscience
authorswithroles_txt_mv	Dumitru A. Iacobas @@aut@@ Sanda Iacobas @@aut@@ Nino Nebieridze @@aut@@ Libor Velíšek @@aut@@ Jana Velíšková @@aut@@
publishDateDaySort_date	2018-01-01T00:00:00Z
hierarchy_top_id	55908109X
id	DOAJ071912908
language_de	englisch
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callnumber-first	R - Medicine
author	Dumitru A. Iacobas
spellingShingle	Dumitru A. Iacobas misc RC321-571 misc beta-estradiol misc cholinergic synapse misc dentate gyrus misc dopaminergic synapse misc GABAergic synapse misc glutamatergic synapse misc Neurosciences. Biological psychiatry. Neuropsychiatry Estrogen Protects Neurotransmission Transcriptome During Status Epilepticus
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topic_title	RC321-571 Estrogen Protects Neurotransmission Transcriptome During Status Epilepticus beta-estradiol cholinergic synapse dentate gyrus dopaminergic synapse GABAergic synapse glutamatergic synapse
topic	misc RC321-571 misc beta-estradiol misc cholinergic synapse misc dentate gyrus misc dopaminergic synapse misc GABAergic synapse misc glutamatergic synapse misc Neurosciences. Biological psychiatry. Neuropsychiatry
topic_unstemmed	misc RC321-571 misc beta-estradiol misc cholinergic synapse misc dentate gyrus misc dopaminergic synapse misc GABAergic synapse misc glutamatergic synapse misc Neurosciences. Biological psychiatry. Neuropsychiatry
topic_browse	misc RC321-571 misc beta-estradiol misc cholinergic synapse misc dentate gyrus misc dopaminergic synapse misc GABAergic synapse misc glutamatergic synapse misc Neurosciences. Biological psychiatry. Neuropsychiatry
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title	Estrogen Protects Neurotransmission Transcriptome During Status Epilepticus
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title_full	Estrogen Protects Neurotransmission Transcriptome During Status Epilepticus
author_sort	Dumitru A. Iacobas
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author_browse	Dumitru A. Iacobas Sanda Iacobas Nino Nebieridze Libor Velíšek Jana Velíšková
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title_sort	estrogen protects neurotransmission transcriptome during status epilepticus
callnumber	RC321-571
title_auth	Estrogen Protects Neurotransmission Transcriptome During Status Epilepticus
abstract	Women with epilepsy commonly have premature onset of menopause. The decrease in estrogen levels is associated with increased occurrence of neurodegenerative processes and cognitive decline. Previously, we found that estradiol (E2) replacement in ovariectomized (OVX) female rats significantly reduced the seizure-related damage in the sensitive hilar region of hippocampal dentate gyrus (DG). However, the complex mechanisms by which E2 empowers the genomic fabrics of neurotransmission to resist damaging effects of status epilepticus (SE) are still unclear. We determined the protective effects of the estradiol replacement against kainic acid-induced SE-associated transcriptomic alterations in the DG of OVX rats. Without E2 replacement, SE altered expression of 44% of the DG genes. SE affected all major functional pathways, including apoptosis (61%), Alzheimer's disease (47%), cell cycle (59%), long-term potentiation (62%), and depression (55%), as well as synaptic vesicle cycle (62%), glutamatergic (53%), GABAergic (49%), cholinergic (52%), dopaminergic (55%), and serotonergic (49%) neurotransmission. However, in rats with E2 replacement the percentage of significantly affected genes after SE was reduced to the average 11% (from 8% for apoptosis to 32% for GABAergic synapse). Interestingly, while SE down-regulated most of the synaptic receptor genes in oil-injected females it had little effect on these receptors after E2-replacement. Our novel Pathway Protection analysis indicated that the E2-replacement prevented SE-related damage from 50% for GABA to 75% for dopaminergic transmission. The 15% synergistic expression between genes involved in estrogen signaling (ESG) and neurotransmission explains why low E2 levels result in down-regulation of neurotransmission. Interestingly, in animals with E2-replacement, SE switched 131 synergistically expressed ESG-neurotransmission gene pairs into antagonistically expressed gene pairs. Thus, the ESG pathway acts like a buffer against SE-induced alteration of neurotransmission that may contribute to the E2-mediated maintenance of brain function after the SE injury in postmenopausal women. We also show that the long-term potentiation is lost in OVX rats following SE but not in those with E2 replacement. The electrophysiological findings in OVX female rats with SE are corroborated by the high percentage of long-term potentiation regulated genes (62%) in oil-injected while only 13% of genes were regulated following SE in E2-replaced rats.
abstractGer	Women with epilepsy commonly have premature onset of menopause. The decrease in estrogen levels is associated with increased occurrence of neurodegenerative processes and cognitive decline. Previously, we found that estradiol (E2) replacement in ovariectomized (OVX) female rats significantly reduced the seizure-related damage in the sensitive hilar region of hippocampal dentate gyrus (DG). However, the complex mechanisms by which E2 empowers the genomic fabrics of neurotransmission to resist damaging effects of status epilepticus (SE) are still unclear. We determined the protective effects of the estradiol replacement against kainic acid-induced SE-associated transcriptomic alterations in the DG of OVX rats. Without E2 replacement, SE altered expression of 44% of the DG genes. SE affected all major functional pathways, including apoptosis (61%), Alzheimer's disease (47%), cell cycle (59%), long-term potentiation (62%), and depression (55%), as well as synaptic vesicle cycle (62%), glutamatergic (53%), GABAergic (49%), cholinergic (52%), dopaminergic (55%), and serotonergic (49%) neurotransmission. However, in rats with E2 replacement the percentage of significantly affected genes after SE was reduced to the average 11% (from 8% for apoptosis to 32% for GABAergic synapse). Interestingly, while SE down-regulated most of the synaptic receptor genes in oil-injected females it had little effect on these receptors after E2-replacement. Our novel Pathway Protection analysis indicated that the E2-replacement prevented SE-related damage from 50% for GABA to 75% for dopaminergic transmission. The 15% synergistic expression between genes involved in estrogen signaling (ESG) and neurotransmission explains why low E2 levels result in down-regulation of neurotransmission. Interestingly, in animals with E2-replacement, SE switched 131 synergistically expressed ESG-neurotransmission gene pairs into antagonistically expressed gene pairs. Thus, the ESG pathway acts like a buffer against SE-induced alteration of neurotransmission that may contribute to the E2-mediated maintenance of brain function after the SE injury in postmenopausal women. We also show that the long-term potentiation is lost in OVX rats following SE but not in those with E2 replacement. The electrophysiological findings in OVX female rats with SE are corroborated by the high percentage of long-term potentiation regulated genes (62%) in oil-injected while only 13% of genes were regulated following SE in E2-replaced rats.
abstract_unstemmed	Women with epilepsy commonly have premature onset of menopause. The decrease in estrogen levels is associated with increased occurrence of neurodegenerative processes and cognitive decline. Previously, we found that estradiol (E2) replacement in ovariectomized (OVX) female rats significantly reduced the seizure-related damage in the sensitive hilar region of hippocampal dentate gyrus (DG). However, the complex mechanisms by which E2 empowers the genomic fabrics of neurotransmission to resist damaging effects of status epilepticus (SE) are still unclear. We determined the protective effects of the estradiol replacement against kainic acid-induced SE-associated transcriptomic alterations in the DG of OVX rats. Without E2 replacement, SE altered expression of 44% of the DG genes. SE affected all major functional pathways, including apoptosis (61%), Alzheimer's disease (47%), cell cycle (59%), long-term potentiation (62%), and depression (55%), as well as synaptic vesicle cycle (62%), glutamatergic (53%), GABAergic (49%), cholinergic (52%), dopaminergic (55%), and serotonergic (49%) neurotransmission. However, in rats with E2 replacement the percentage of significantly affected genes after SE was reduced to the average 11% (from 8% for apoptosis to 32% for GABAergic synapse). Interestingly, while SE down-regulated most of the synaptic receptor genes in oil-injected females it had little effect on these receptors after E2-replacement. Our novel Pathway Protection analysis indicated that the E2-replacement prevented SE-related damage from 50% for GABA to 75% for dopaminergic transmission. The 15% synergistic expression between genes involved in estrogen signaling (ESG) and neurotransmission explains why low E2 levels result in down-regulation of neurotransmission. Interestingly, in animals with E2-replacement, SE switched 131 synergistically expressed ESG-neurotransmission gene pairs into antagonistically expressed gene pairs. Thus, the ESG pathway acts like a buffer against SE-induced alteration of neurotransmission that may contribute to the E2-mediated maintenance of brain function after the SE injury in postmenopausal women. We also show that the long-term potentiation is lost in OVX rats following SE but not in those with E2 replacement. The electrophysiological findings in OVX female rats with SE are corroborated by the high percentage of long-term potentiation regulated genes (62%) in oil-injected while only 13% of genes were regulated following SE in E2-replaced rats.
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title_short	Estrogen Protects Neurotransmission Transcriptome During Status Epilepticus
url	https://doi.org/10.3389/fnins.2018.00332 https://doaj.org/article/9ba7cc7b79d4490f8cd0a694de2b26b8 https://www.frontiersin.org/article/10.3389/fnins.2018.00332/full https://doaj.org/toc/1662-453X
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author2	Dumitru A. Iacobas Sanda Iacobas Nino Nebieridze Libor Velíšek Jana Velíšková
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up_date	2024-07-03T22:50:43.350Z
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