Kinetics of semax penetration into the brain and blood of rats after its intranasal administration

Шевченко, К. В.; Nagaev, I. Yu.; Alfeeva, L. Yu.; Андреева, Л. А.; Каменский, А. А.; Levitskaya, N. G.; Шевченко, В. П.; Grivennikova, I. A.; Myasoedov, N. F.

doi:10.1134/s1068162006010055

Cited by 15 publications

(11 citation statements)

References 6 publications

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“…It seems that treatment with Semax leads to changes in the transcription of neurotrophins and their receptors specifically in the ischemic rat cortex, whereas the influence of PGP was mainly unspecific and more broadly affected gene activity in rats without surgery, sham-operated rats and rats subjected to pMCAO. It should be mentioned that Semax undergoes rapid enzymatic degradation resulting in a mixture of different derivative peptides (Shevchenko et al 2006). PGP was predominant in the brain tissues 1 h after the Semax intranasal injection.…”

Section: Neurotrophin Receptor Mrna Expression In the Cortex Of Rats mentioning

confidence: 99%

Semax and Pro-Gly-Pro Activate the Transcription of Neurotrophins and Their Receptor Genes after Cerebral Ischemia

Дмитриева

Povarova²,

Skvortsova³

et al. 2009

Cell Mol Neurobiol

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Consisting of a fragment of ACTH(4-7) and C-terminal PGP tripeptide, the polypeptide Semax is successfully used for acute stroke therapy. Previous experiments showed rapid induction of Bdnf, Ngf, and TrkB expression in intact rat hippocampus following Semax treatment. To investigate the mRNA expression of neurotrophins and their receptors after treatment with either Semax or PGP, the rat brains were analyzed at three time points following a permanent middle cerebral artery occlusion (pMCAO). We have shown for the first time that both Semax and PGP activate the transcription of neurotrophins and their receptors in the cortex of rats subjected to pMCAO. The profiles of transcription alteration under PGP and Semax treatment were partially overlapped. Semax enhanced the transcription of Bdnf, TrkC, and TrkA 3 h after occlusion, Nt-3 and Ngf 24 h after occlusion, and Ngf 72 h after occlusion. PGP enhanced the transcription of Bdnf and TrkC 3 h after pMCAO and Ngf, TrkB, TrkC, and TrkA 24 h after pMCAO. The analysis of the transcription alterations under PGP and Semax treatment in the cortex of rats without surgery, sham-operated rats and rats subjected to pMCAO revealed that Semax selectively affected the transcription of neurotrophins and their receptors in the ischemic rat cortex, whereas the influence of PGP was mainly unspecific.

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Section: Neurotrophin Receptor Mrna Expression In the Cortex Of Rats mentioning

confidence: 99%

Semax and Pro-Gly-Pro Activate the Transcription of Neurotrophins and Their Receptor Genes after Cerebral Ischemia

Дмитриева

Povarova²,

Skvortsova³

et al. 2009

Cell Mol Neurobiol

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“…Many compounds are degraded by cytochrome P450 systems as a result of the oxidation of organic compounds by molecular O 2 [15]. For example, it was shown that the content of Semax in rat brain reached a maximum already after 2 min [12]. Then, Semax underwent rapid proteolysis so that its content fell by 12 times after 30 min.…”

Section: Resultsmentioning

confidence: 99%

“…Owing to a circulatory system in the brain and because a part of the intranasally administered peptide entered the circulation, its presence was calculated by a previously described method [12,13].…”

Section: Experimental Partmentioning

confidence: 99%

Proteolysis of Pro-Gly-Pro-Leu in Rat-Brain Hippocampus, Cerebellum, and Cortex Upon Intranasal Administration

et al. 2015

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The concentrations of Pro-Gly-Pro-Leu (PGPL) tetrapeptide and its metabolites (Gly-Pro-Leu, Pro-Gly-Pro, Gly-Pro, and Pro-Gly) in various rat-brain compartments (hippocampus, cerebellum, cortex) were shown to be time-dependent after intranasal administration. The maximum concentrations of [ 3 H]-labeled PGPL and its degradation products in rat brain were observed after 40 min and amounted to 0.07% of the administered dose. The maximum concentrations of PGPL in the cerebellum, hippocampus, and cortex were 2.37, 1.93, and 0.67 pmol/g, respectively. The distribution in these brain compartments of PGPL proteolysis products differed from that of the initial peptide. The greatest amount of Gly-Pro-Leu was observed in the hippocampus with less in the cerebellum and cortex; of glyprolines (Pro-Gly-Pro, Pro-Gly, and Gly-Pro), in the cerebellum with less in the hippocampus and cortex. The contribution of one PGPL metabolic pathway or another to the formation from it of the set of shorter peptides in various rat-brain compartments was estimated based on the results.

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“…Pharmacokinetic investigation of Semax demonstrated that ten to 15 times higher content of Semax can be found in the brain 2 min after its intranasal administration in comparison with its injection in blood. A higher content of Semax in the rat brain and blood was observed for the first minute after its intranasal administration (Shevchenko et al 2006).…”

Section: Discussionmentioning

confidence: 98%

Comparison of the Temporary Dynamics of NGF and BDNF Gene Expression in Rat Hippocampus, Frontal Cortex, and Retina Under Semax Action

et al. 2009

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Neurotrophins are a family of structurally related proteins that regulate the survival, differentiation, and maintenance of function of different neuron populations. Some peptides are able to affect the production and activity of neurotrophins. One of these synthetic peptides is heptapeptide Semax, an analog of the N-terminal adrenocorticotropic hormone fragment 4-10. It is known that Semax has effects on learning and memory formation and exerts some neuroprotective effects in rodents and humans. Male Wistar rats were treated for 20 min, 40 min, 90 min, 3 h, 8 h, and 24 h with Semax. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) gene expression in rat brain and retina was analyzed by real-time polymerase chain reaction. It was revealed that after Semax administration the multidirectional activation of the expression of the genes under investigation in the hippocampus, frontal cortex, and retina was observed. The expression of both neurotrophin genes was decreased in rat hippocampus and retina 20 min after Semax administration and was increased in the frontal cortex. The expression levels of NGF remained practically constant in the retina at the initial stage, whereas the expression levels of BDNF were significantly increased 90 min after Semax administration.

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Kinetics of semax penetration into the brain and blood of rats after its intranasal administration

Cited by 15 publications

References 6 publications

Semax and Pro-Gly-Pro Activate the Transcription of Neurotrophins and Their Receptor Genes after Cerebral Ischemia

Semax and Pro-Gly-Pro Activate the Transcription of Neurotrophins and Their Receptor Genes after Cerebral Ischemia

Proteolysis of Pro-Gly-Pro-Leu in Rat-Brain Hippocampus, Cerebellum, and Cortex Upon Intranasal Administration

Comparison of the Temporary Dynamics of NGF and BDNF Gene Expression in Rat Hippocampus, Frontal Cortex, and Retina Under Semax Action

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