Antistress Action of Melanocortin Derivatives Associated with Correction of Gene Expression Patterns in the Hippocampus of Male Rats Following Acute Stress.

Filippenkov IB, Stavchansky VV, Glazova NY, Sebentsova EA, Remizova JA, Valieva LV, Levitskaya NG, Myasoedov NF, Limborska SA, Dergunova LV

International journal of molecular sciences17 Sept 2021Cited by 7 (Europe PMC)

PMID34576218PMCIDPMC8469576DOI10.3390/ijms221810054PepBankPUB-34576218

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Summary

Natural melanocortins (MCs) have been used in the successful development of drugs with neuroprotective properties. Here, we studied the behavioral effects and molecular genetic mechanisms of two synthetic MC derivatives-ACTH(4-7)PGP (Semax) and ACTH(6-9)PGP under normal and acute restraint stress (ARS) conditions. Administration of Semax or ACTH(6-9)PGP (100 μg/kg) to rats 30 min before ARS attenuated ARS-induced behavioral alterations. Using high-throughput RNA sequencing (RNA-Seq), we identified 1359 differentially expressed genes (DEGs) in the hippocampus of vehicle-treated rats subjected to ARS, using a cutoff of >1.5 fold change and adjusted p-value (Padj) < 0.05, in samples collected 4.5 h after the ARS. Semax administration produced > 1500 DEGs, whereas ACTH(6-9)PGP administration led to <400 DEGs at 4.5 h after ARS. Nevertheless, ~250 overlapping DEGs were identified, and expression of these DEGs was changed unidirectionally by both peptides under ARS conditions. Modulation of the expression of genes associated with biogenesis, translation of RNA, DNA replication, and immune and nervous system function was produced by both peptides. Furthermore, both peptides upregulated the expression levels of many genes that displayed decreased expression after ARS, and vice versa, the MC peptides downregulated the expression levels of genes that were upregulated by ARS. Consequently, the antistress action of MC peptides may be associated with a correction of gene expression patterns that are disrupted during ARS.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

2 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In male rats, Semax given 30 min before acute restraint stress attenuated stress-induced behavioral alterations.
In plain wordsIn rats, Semax given before a stress test reduced the behaviour changes that the stress caused.
Peptide
Semax
Outcome
DecreaseARS-induced behavioral alterations
Study
ratn: not reported in source
acute restraint stress (ARS), hippocampus
Outcome group
Anxiety and mood · Mental health and mood
Studied dose
100 μg/kgAs given in this study (rat).
Source sentences
Summary
Administration of Semax or ACTH(6-9)PGP (100 μg/kg) to rats 30 min before ARS attenuated ARS-induced behavioral alterations.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we studied the behavioral effects and molecular genetic mechanisms of two synthetic MC derivatives-ACTH(4-7)PGP (Semax) and ACTH(6-9)PGP under normal and acute restraint stress (ARS) conditions.
Show in the study text Report a problemFND-3457621801
02AnimalAnimal study (in vivo)Mechanism
In male rats after acute restraint stress, Semax produced more than 1500 differentially expressed genes in the hippocampus at 4.5 h.
In plain wordsIn rats after a stress test, Semax changed the activity of more than 1500 genes in the hippocampus.
Peptide
Semax
Outcome
MixedDifferentially expressed genes in hippocampus after ARS
Study
ratn: not reported in source
acute restraint stress (ARS), hippocampus
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
100 μg/kgAs given in this study (rat).
Measurements
Differentially expressed genes
> 1500 genes
Semax, hippocampus, 4.5 h after ARS
Source sentences
Summary
Semax administration produced > 1500 DEGs
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we studied the behavioral effects and molecular genetic mechanisms of two synthetic MC derivatives-ACTH(4-7)PGP (Semax) and ACTH(6-9)PGP under normal and acute restraint stress (ARS) conditions.
Show in the study text Report a problemFND-3457621802

Studies that did not test the peptide alone3

In this study, Semax was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Semax.

03AnimalNot a test of Semax aloneAnimal study (in vivo)Mechanism
In male rats after acute restraint stress, about 250 differentially expressed genes overlapped between Semax and ACTH(6-9)PGP and changed in the same direction.
In plain wordsIn rats after a stress test, about 250 genes changed in the same direction with both peptides.
Peptide
Semax
Outcome
Not applicableOverlapping differentially expressed genes shared with ACTH(6-9)PGP
Study
ratn: not reported in source
acute restraint stress (ARS), hippocampus
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Measurements
Overlapping differentially expressed genes
≈ 250 genes
Semax and ACTH(6-9)PGP, ARS
Source sentences
Summary
Nevertheless, ~250 overlapping DEGs were identified, and expression of these DEGs was changed unidirectionally by both peptides under ARS conditions.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we studied the behavioral effects and molecular genetic mechanisms of two synthetic MC derivatives-ACTH(4-7)PGP (Semax) and ACTH(6-9)PGP under normal and acute restraint stress (ARS) conditions.
In this study, Semax was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semax.
Show in the study text Report a problemFND-3457621803
04AnimalNot a test of Semax aloneAnimal study (in vivo)Mechanism
In male rats after acute restraint stress, both peptides modulated genes linked to biogenesis, RNA translation, DNA replication and immune and nervous system function.
In plain wordsIn rats after a stress test, both peptides changed genes linked to cell building, gene reading, and immune and nerve function.
Peptide
Semax
Outcome
Not applicableBiological functions of modulated genes
Study
ratn: not reported in source
acute restraint stress (ARS), hippocampus
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
Modulation of the expression of genes associated with biogenesis, translation of RNA, DNA replication, and immune and nervous system function was produced by both peptides.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we studied the behavioral effects and molecular genetic mechanisms of two synthetic MC derivatives-ACTH(4-7)PGP (Semax) and ACTH(6-9)PGP under normal and acute restraint stress (ARS) conditions.
In this study, Semax was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semax.
Show in the study text Report a problemFND-3457621804
05AnimalNot a test of Semax aloneAnimal study (in vivo)Mechanism
In male rats after acute restraint stress, both peptides raised the expression of many genes decreased by stress and lowered the expression of genes raised by stress.
In plain wordsIn rats after a stress test, both peptides moved many stress-disturbed genes back in the opposite direction.
Peptide
Semax
Outcome
MixedCorrection of ARS-disrupted gene expression
Study
ratn: not reported in source
acute restraint stress (ARS), hippocampus
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
Furthermore, both peptides upregulated the expression levels of many genes that displayed decreased expression after ARS, and vice versa, the MC peptides downregulated the expression levels of genes that were upregulated by ARS.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, we studied the behavioral effects and molecular genetic mechanisms of two synthetic MC derivatives-ACTH(4-7)PGP (Semax) and ACTH(6-9)PGP under normal and acute restraint stress (ARS) conditions.
In this study, Semax was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semax.
Show in the study text Report a problemFND-3457621805

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
9 Oct 2026, 19:08 UTC
Study results updated
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC

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