Synthetic Adrenocorticotropic Peptides Modulate the Expression Pattern of Immune Genes in Rat Brain following the Early Post-Stroke Period
Ischemic stroke is an acute local decrease in cerebral blood flow due to a thrombus or embolus. Of particular importance is the study of the genetic systems that determine the mechanisms underlying the formation and maintenance of a therapeutic window (a time interval of up to 6 h after a stroke) wh...
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MDPI AG
2023-06-01
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| author | Ivan B. Filippenkov Julia A. Remizova Vasily V. Stavchansky Alina E. Denisova Leonid V. Gubsky Nikolay F. Myasoedov Svetlana A. Limborska Lyudmila V. Dergunova |
| author_facet | Ivan B. Filippenkov Julia A. Remizova Vasily V. Stavchansky Alina E. Denisova Leonid V. Gubsky Nikolay F. Myasoedov Svetlana A. Limborska Lyudmila V. Dergunova |
| author_sort | Ivan B. Filippenkov |
| collection | DOAJ |
| description | Ischemic stroke is an acute local decrease in cerebral blood flow due to a thrombus or embolus. Of particular importance is the study of the genetic systems that determine the mechanisms underlying the formation and maintenance of a therapeutic window (a time interval of up to 6 h after a stroke) when effective treatment can be provided. Here, we used a transient middle cerebral artery occlusion (tMCAO) model in rats to study two synthetic derivatives of adrenocorticotropic hormone (ACTH). The first was ACTH(4-7)PGP, which is known as Semax. It is actively used as a neuroprotective drug. The second was the ACTH(6-9)PGP peptide, which is elucidated as a prospective agent only. Using RNA-Seq analysis, we revealed hundreds of ischemia-related differentially expressed genes (DEGs), as well as 131 and 322 DEGs related to the first and second peptide at 4.5 h after tMCAO, respectively, in dorsolateral areas of the frontal cortex of rats. Furthermore, we showed that both Semax and ACTH(6-9)PGP can partially prevent changes in the immune- and neurosignaling-related gene expression profiles disturbed by the action of ischemia at 4.5 h after tMCAO. However, their different actions with regard to predominantly immune-related genes were also revealed. This study gives insight into how the transcriptome depends on the variation in the structure of the related peptides, and it is valuable from the standpoint of the development of measures for early post-stroke therapy. |
| first_indexed | 2024-03-11T01:03:07Z |
| format | Article |
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| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T01:03:07Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-ce9f00a3cf674f87b0345781aff7c7082023-11-18T19:29:37ZengMDPI AGGenes2073-44252023-06-01147138210.3390/genes14071382Synthetic Adrenocorticotropic Peptides Modulate the Expression Pattern of Immune Genes in Rat Brain following the Early Post-Stroke PeriodIvan B. Filippenkov0Julia A. Remizova1Vasily V. Stavchansky2Alina E. Denisova3Leonid V. Gubsky4Nikolay F. Myasoedov5Svetlana A. Limborska6Lyudmila V. Dergunova7Institute of Molecular Genetics of National Research Center “Kurchatov Institute”, Kurchatov Sq. 2, Moscow 123182, RussiaInstitute of Molecular Genetics of National Research Center “Kurchatov Institute”, Kurchatov Sq. 2, Moscow 123182, RussiaInstitute of Molecular Genetics of National Research Center “Kurchatov Institute”, Kurchatov Sq. 2, Moscow 123182, RussiaDepartment of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University, Ostrovitianov Str. 1, Moscow 117997, RussiaDepartment of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University, Ostrovitianov Str. 1, Moscow 117997, RussiaInstitute of Molecular Genetics of National Research Center “Kurchatov Institute”, Kurchatov Sq. 2, Moscow 123182, RussiaInstitute of Molecular Genetics of National Research Center “Kurchatov Institute”, Kurchatov Sq. 2, Moscow 123182, RussiaInstitute of Molecular Genetics of National Research Center “Kurchatov Institute”, Kurchatov Sq. 2, Moscow 123182, RussiaIschemic stroke is an acute local decrease in cerebral blood flow due to a thrombus or embolus. Of particular importance is the study of the genetic systems that determine the mechanisms underlying the formation and maintenance of a therapeutic window (a time interval of up to 6 h after a stroke) when effective treatment can be provided. Here, we used a transient middle cerebral artery occlusion (tMCAO) model in rats to study two synthetic derivatives of adrenocorticotropic hormone (ACTH). The first was ACTH(4-7)PGP, which is known as Semax. It is actively used as a neuroprotective drug. The second was the ACTH(6-9)PGP peptide, which is elucidated as a prospective agent only. Using RNA-Seq analysis, we revealed hundreds of ischemia-related differentially expressed genes (DEGs), as well as 131 and 322 DEGs related to the first and second peptide at 4.5 h after tMCAO, respectively, in dorsolateral areas of the frontal cortex of rats. Furthermore, we showed that both Semax and ACTH(6-9)PGP can partially prevent changes in the immune- and neurosignaling-related gene expression profiles disturbed by the action of ischemia at 4.5 h after tMCAO. However, their different actions with regard to predominantly immune-related genes were also revealed. This study gives insight into how the transcriptome depends on the variation in the structure of the related peptides, and it is valuable from the standpoint of the development of measures for early post-stroke therapy.https://www.mdpi.com/2073-4425/14/7/1382ischemic strokeRNA-SeqACTH(4-7)PGPACTH(6-9)PGPtMCAOgene expression |
| spellingShingle | Ivan B. Filippenkov Julia A. Remizova Vasily V. Stavchansky Alina E. Denisova Leonid V. Gubsky Nikolay F. Myasoedov Svetlana A. Limborska Lyudmila V. Dergunova Synthetic Adrenocorticotropic Peptides Modulate the Expression Pattern of Immune Genes in Rat Brain following the Early Post-Stroke Period Genes ischemic stroke RNA-Seq ACTH(4-7)PGP ACTH(6-9)PGP tMCAO gene expression |
| title | Synthetic Adrenocorticotropic Peptides Modulate the Expression Pattern of Immune Genes in Rat Brain following the Early Post-Stroke Period |
| title_full | Synthetic Adrenocorticotropic Peptides Modulate the Expression Pattern of Immune Genes in Rat Brain following the Early Post-Stroke Period |
| title_fullStr | Synthetic Adrenocorticotropic Peptides Modulate the Expression Pattern of Immune Genes in Rat Brain following the Early Post-Stroke Period |
| title_full_unstemmed | Synthetic Adrenocorticotropic Peptides Modulate the Expression Pattern of Immune Genes in Rat Brain following the Early Post-Stroke Period |
| title_short | Synthetic Adrenocorticotropic Peptides Modulate the Expression Pattern of Immune Genes in Rat Brain following the Early Post-Stroke Period |
| title_sort | synthetic adrenocorticotropic peptides modulate the expression pattern of immune genes in rat brain following the early post stroke period |
| topic | ischemic stroke RNA-Seq ACTH(4-7)PGP ACTH(6-9)PGP tMCAO gene expression |
| url | https://www.mdpi.com/2073-4425/14/7/1382 |
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