Novel Insights into the Protective Properties of ACTH<sub>(4-7)</sub>PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats.
Filippenkov. Ivan B IB; Stavchansky. Vasily V VV; Denisova. Alina E AE; Yuzhakov. Vadim V VV; Sevan'kaeva. Larisa E LE; Sudarkina. Olga Y OY; Dmitrieva. Veronika G VG; Gubsky. Leonid V LV; Myasoedov. Nikolai F NF; Limborska. Svetlana A SA; Dergunova. Lyudmila V LV
Key Findings
- Semax altered expression of 394 genes in the rat brain 24 hours after induced ischemia‑reperfusion.
- Inflammation‑related genes were suppressed by Semax, while neurotransmission‑related genes were activated.
- Ischemia‑reperfusion without Semax showed the reverse pattern: increased inflammation genes and decreased neurotransmission genes.
Practical Outcomes
- Semax shows promise as a neuroprotective agent that can counteract inflammation and support nerve signaling after a stroke, at least in rats. However, the study provides no human dosage, safety, or protocol information, so it isn’t ready for self‑experimentation. For biohackers, the main takeaway is that Semax may have brain‑protective properties, but more clinical research is needed before considering any real‑world use.
Summary
In rats that had a brief brain blood‑flow blockage (a model of stroke), the peptide Semax changed the brain’s gene activity: it lowered inflammation‑related genes and boosted genes involved in nerve signaling. This pattern was the opposite of what happened with the blockage alone, suggesting Semax may help protect the brain after such injury.
Abstract
Cerebral ischaemia is the most common cause of impaired brain function. Biologically active peptides represent potential drugs for reducing the damage that occurs after ischaemia. The synthetic melanocortin derivative, ACTH<sub>(4-7)</sub>PGP (Semax), has been used successfully in the treatment of patients with severe impairment of cerebral blood circulation. However, its molecular mechanisms of action within the brain are not yet fully understood. Previously, we used the transient middle cerebral artery occlusion (tMCAO) model to study the damaging effects of ischaemia-reperfusion on the brain transcriptome in rats. Here, using RNA-Seq analysis, we investigated the protective properties of the Semax peptide at the transcriptome level under tMCAO conditions. We have identified 394 differentially expressed genes (DEGs) (>1.5-fold change) in the brains of rats at 24 h after tMCAO treated with Semax relative to saline. Following tMCAO, we found that Semax suppressed the expression of genes related to inflammatory processes and activated the expression of genes related to neurotransmission. In contrast, ischaemia-reperfusion alone activated the expression of inflammation-related genes and suppressed the expression of neurotransmission-related genes. Therefore, the neuroprotective action of Semax may be associated with a compensation of mRNA expression patterns that are disrupted during ischaemia-reperfusion conditions.
Study Information
pubmed
2020
2020-06-22T00:00:00.000Z
10.3390/genes11060681
24
66