Cortexin

Transcriptomic analysis reveals pathway-specific targets for hyperlocomotion and social withdrawal in mouse models of schizophrenia.

Xu Liu, Lin Yuan, Qian Chu +4 more

Schizophreniais a severe mental disorder with complex behavioral pathology and complexgenetic risk.Here, we performed an integrated transcriptomic analysis of the prefrontal cortexin two distinct male C57BL/6J mouse modelsof schizophrenia,the neurodevelopmental methylazoxymethanol acetate (MAM) model (n = 7) and the acute non-competitive N-methyl-D-aspartatereceptor (NMDAR) antagonist MK-801model (n = 6, control n  = 8),compared to that of human patients. Differentially expressed genes in the MK-801 model displayed a modest correlation with that of schizophrenia patients (r = 0.40, p = 2.7 × 10-6), higher than the MAM model (r = 0.15, p = 0.23), underscoring NMDAR antagonism's relevance to the core pathology of the disorder. Using weighted gene co-expression network analysis, we identified 28co-expression modules across the mouse models, with 11modules significantly associated with individual schizophrenia-related behavioral endophenotypes.Notably, the brown module (linked to hyperlocomotion, r = 0.55, p = 0.01) and the darkgrey module (associated with social withdrawal, r = -0.71, p = 3 × 10-4)were enriched in Wnt and PI3K/Akt signaling pathways, respectively.Pharmacological inhibition of these two pathways specifically rectified corresponding behavioral anomalies in the MK-801 model, highlighting the critical role of altered Wnt and PI3K/Akt signaling in these behavioral domains of schizophrenia-related behaviors and proposing new avenues for therapeutic intervention.

[Multimodal therapeutic strategies in the treatment of cerebrovascular disease].

A I Fedin, E N Saverskaya, K R Badalyan

The review presents the scientific substantiation of the relationship between age-related cerebrovascular changes and dysregulation of cerebral perfusion, blood-brain barrier (BBB) function and neurovascular units. The ischemic cascade in cerebrovascular disease (CVD) is considered, the main links of which are glutamate excitoxicosis, oxidative stress and neuroinflammation. Endothelial dysfunction and increased BBB permeability play an important role in the development of neuroinflammation. The use of multifunctional drugs aimed at various pathological targets of acute and chronic cerebral ischemia for the purpose of neuroprotection has been substantiated. These drugs include the peptide Cortexin (cattle cerebral cortex polypeptides). Experimental data on the study of its molecular partners in the brain are presented. The clinical efficacy of Cortexin as a neuroprotective drug in CVD has been established in many studies.

[Comparative study of protective effects of Cortexin, Cerebrolysin and Actovegin on memory impairment, cerebral circulation and morphological changes in the hippocampus of rats with chronic brain ischemia].

I N Tyurenkov, D V Kurkin, A V Kalatanova +8 more

To compare the effects of cortexin, cerebrolysin and actovegin on memory impairment, cerebral circulation and morphological changes in the hippocampus of rats with chronic brain ischemia.

[Epigenetic Mechanisms of Peptide-Driven Regulation and Neuroprotective Protein FKBP1b].

B I Kuznik, S O Davydov, E S Popravka +3 more

Cortexin is a clinically approved cerebral cortex polypeptide complex in calves. The mechanism of cortexin action is not understood well. Two cortexin derivatives, short peptides EDR and DS with neuroprotective activity, were synthesized. According to the data of molecular modeling, these peptides are able to bind to the histone H1.3 protein. This can affect the conformation of histone H1.3, which leads to a change in the chromatin structure in the loci of some genes, in particular Fkbp1b encoding the FK506-binding protein. Electrophysiological processes associated with the Ca^(2+) exchange are disturbed in the pyramidal neurons of the hippocampus during aging of the brain. The Fkbp1b gene encodes peptidyl-prolyl cis-trans isomerase, regulating the release of calcium ions from the sarcoplasmic and endoplasmic reticulum of neurons. The activation of the Fkbp1b gene transcription under treatment with short peptides can promote the synthesis of its protein product and the activation of the Ca^(2+) release from organelles of the sarcoplasmic and endoplasmic reticulum of neurons, which, in turn, can lead to an increase in the functional activity of neurons.

[Clinical efficacy of neuropeptides in cerebrovascular pathology].

O A Shavlovskaya

Great value in the treatment of ischemic stroke (IS) is given for neuroprotection. When ischemic neuroprotection aims to increase the period of 'therapeutic window' and stop the cascade of pathological reactions. The neuroprotection is defined as the continuous adaptation of the neuron to new functional conditions, as the key to reducing damage to brain tissue caused by ischemia, it acts at the level of the molecular cascade leading to the dysfunction and death of neurons. Special attention is paid to the study of the properties of low molecular weight neuropeptides that penetrate through the hematoencephalitic barrier and exert a multiple effect on the Central nervous system (CNS) even in small concentrations. One of neuropeptide of cytoprotectors, is Cortexin, containing a complex of low molecular weight peptides (with mass from 1 to 10 kDa), which is optimally balanced and close to the metabolism of brain neurons (organotropic) that exert tissue-specific, regulatory and restorative effect on the cerebral cortex. The article presents data on the effectiveness purpose of Cortexin in patients with IS. It is shown that the optimal scheme for the purpose of Cortexin includes: intramuscular administration of Cortexin in the dose of 20 mg (10 mg morning + 10 mg evening) for 10 days, with a repeat the same course within 10 days after the first, since the first 6 h after the onset of stroke symptoms. The observation period is more than 2 months.

[Cortexin. Molecular mechanisms and targets of neuroprotective activity].

O A Gomazkov

Neurotrophic drug cortexin, a lyophilized extraction of animal cortex, comprises neuropeptides, amino acids and trace elements. The nucleoprotein complexes of the cerebral cortex can also retain elements of chromatin with DNA fragments. All of these components of cortexin have a specific range of "targets" for the specific correction of the molecular and cellular processes at various stages of the pathological process. A modern concept of neurosignaling considers the associated processes - from the synaptic level to the epigenetic patterns of neuron nucleus, in which an important place belongs to corrective peptide molecules. Peptide components of cortexin derived from the animal brain, which interact with cellular and molecular "targets", provide a new view on mechanisms of neuroprotection.

[Histostructural changes of rat cerebral cortex during hemorrhagic stroke modeling].

S I Savos'ko, Iu B Chaĭkovs'kyĭ, N Kh Pogoriela +1 more

Pathological changes during modeling of primary and secondary acute hemorrhagic stroke were studied in rats. We revealed differences in the activity of pharmacological action of medications under condition of acute stroke. The action of medications increased viability of neurons in both hemispheres of rat cerebrum at a right-side primary and secondary hemorrhagic stroke. Following secondary stroke, the amount of degenerative neurons amounted 25.5 +/- 0.8 cells/mm2, following the action ofcerebrolysin this value was 17.6 +/- 1.7 cells/ mm2 and after the action of cortexine and cerebral this value amounted 18.0 +/- 0.9 cells/mm2 and 10.7 +/- 0.4 cells/ mm2, respectively. In control animals the number of degenerative neurons did not exceed 2% and averaged 1.5 +/- 0.1 cells/mm2. Analysis of the morphological and statistical data showed that the most effective remedies under the primary and secondary hemorrhagic insult are cortexine and cerebral. Cerebral was found to be more effective.