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22 days ago
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Cognitive impairment is a group of disorders that affect brain cognitive function, including symptoms such as memory loss, difficulty concentrating, and decreased thinking ability, which severely impact patients' quality of life. Neuropeptide Sema, as a substance with multiple regulatory effects on the nervous system, is helpful in treating epilepsy, improving cognitive function, and alleviating acute stress.
Figure 1 The chemical structure of Sema.
Overview of Neuropeptide Sema
Sema is a synthetic heptapeptide with the chemical structure Met - Glu - His - Phe - Pro - Gly - Pro. It is an analog of the 4-10 fragment of adrenocorticotropic hormone (ACTH) and can interact with specific receptors in the central nervous system to exert a series of biological effects. Due to its direct action on the central nervous system and lack of hormonal activity, it has laid the foundation for its application in the field of neuroscience.
Mechanism of Action of Neuropeptide Sema on Cognitive Function
Regulation of Neurotransmitter Systems: Sema may improve cognitive function by influencing the release, synthesis, or metabolism of neurotransmitters. It can regulate the levels of neurotransmitters such as dopamine and acetylcholine. Dopamine plays a key role in cognitive processes such as attention, learning, and memory. Sema may promote the activity of dopaminergic neurons, increase dopamine release, and thereby enhance the brain's ability to process and integrate information. Acetylcholine is a neurotransmitter closely associated with learning and memory. Sema may improve the function of the cholinergic nervous system by regulating the synthesis or release of acetylcholine, thereby enhancing cognitive function.
Promoting neurogenesis: Sema can stimulate the proliferation and differentiation of neural stem cells, promoting the generation of new neurons. In brain regions such as the hippocampus, which are closely associated with learning and memory, the generation of new neurons is crucial for maintaining normal cognitive function. Sema may promote neurogenesis in the hippocampus by activating specific signaling pathways, such as the Wnt/β-catenin signaling pathway, which plays a key role in the proliferation, differentiation, and survival of neural stem cells, thereby providing a structural foundation for cognitive enhancement.
Figure 2 The Potency of Sema Peptide Therapy toward MDA Level and Protein Profile in Epilepsy Rats (Rattus norvegicus). M is marker; A is Group A (negative control); B is group B (positive control); and C is group C (semax peptide therapy).
Antioxidant effects: Oxidative stress plays a significant role in neurodegenerative diseases and cognitive decline. Sema possesses antioxidant properties, enabling it to scavenge excess free radicals in the body and reduce oxidative damage to neurons. For example, by enhancing the activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and reducing the levels of oxidative products like malondialdehyde (MDA), it protects the integrity of neuronal membranes and maintains normal neuronal function, thereby indirectly contributing to improved cognitive function.
Regulating gene expression: Sema can influence the expression of genes related to cognitive function. It may upregulate the gene expression of certain neurotrophic factors and their receptors, such as brain-derived neurotrophic factor (BDNF) and its receptor TrkB. BDNF is crucial for neuronal survival, differentiation, synaptic plasticity, and learning and memory processes. Sema enhances cognitive function by promoting BDNF expression, thereby strengthening neuronal connections and signal transmission.
Applications of the neuropeptide Sema in cognitive enhancement
Preclinical studies
Animal experiments: In numerous animal experiments, Sema demonstrated significant cognitive-enhancing effects. In the Morris water maze test, rats treated with Sema were able to locate the hidden platform more quickly and spent more time in the target quadrant during the memory testing phase, indicating improved spatial learning and memory abilities. In the novel object recognition test, animals treated with Sema exhibited a significant increase in exploration time for new objects, indicating improved object recognition memory. These experimental results suggest that Sema can effectively enhance animals' learning and memory abilities.
Cell experiments: At the cellular level, Sema has a positive impact on neuronal cell survival, proliferation, and differentiation. Cultured neuronal cells exposed to oxidative stress or other damaging factors showed significantly improved cell survival rates when treated with Sema, promoting neuronal axon growth and branching, and enhancing neuronal connections. These cellular experiment results provide a cellular basis for Sema's cognitive-enhancing effects at the whole-animal level.
Figure 3 Micrograph of hippocampal dentate area sections immunohistochemically stained with antibodies against the Ki-67 protein: (a) 14-day-old KM rat injected with Sema on days 7–11 after birth and (b) intact 14-day-old KM rat. Scale, 100 µm.
Clinical application exploration
Cognitive impairments associated with neurological disorders: For certain neurological disorders, such as Alzheimer's disease and Parkinson's disease, which are accompanied by cognitive impairments, Sema holds potential therapeutic value. In some small-scale clinical trials, patients with mild to moderate Alzheimer's disease who received Sema treatment for a period of time showed improvements in memory, attention, and executive function, as assessed by cognitive function scales. This may be due to Sema's multiple mechanisms of action, which reduce neuronal damage, promote neural repair and regeneration, and thereby improve patients' cognitive function.
Cognitive Enhancement in Healthy Populations: In addition to addressing cognitive impairments in disease states, Sema may also have cognitive-enhancing effects in healthy populations. With the accelerating pace of modern life and increasing work-related stress, there is growing demand for enhancing cognitive abilities. Some studies have explored the effects of Sema in healthy volunteers. For example, in a study involving healthy adults, cognitive tests conducted after administering Sema to participants revealed improvements in attention, working memory, and information processing speed. This suggests that Sema may serve as a “smart drug” to help healthy individuals enhance cognitive performance in specific situations, such as preparing for exams or handling high-intensity work.
Current Status and Prospects of Sema Research
Current Status: Currently, research on Sema has achieved certain results. In basic research, its mechanism of action has been relatively well understood; in preclinical studies, its cognitive-enhancing effects in animal models have been confirmed; and in clinical studies, it has shown preliminary potential in treating cognitive disorders.
Conclusion
In summary, neuropeptide Sema, as a substance with potential cognitive-enhancing effects, has demonstrated efficacy in both basic research and clinical applications.
Sources
[1] Glazova N Y, Manchenko D M, Vilensky D A, et al. Effects of Sema in the Rat Models of Acute Stress[J]. Journal of Evolutionary Biochemistry and Physiology, 2023,59(1):200-212.DOI:10.1134/S0022093023010179.
[2] Hadarceva K, Belyaeva E. SEMAX - APPLICATION PROSPECTS (brief overview message)[J]. Clinical Medicine and Pharmacology, 2021. https://api.semanticscholar.org/CorpusID:245468513
[3] Puspita R, Pratamastuti D, Safitri A, et al. The Potency of Sema Peptide Therapy toward MDA Level and Protein Profile in Epilepsy Rats (Rattus norvegicus), 2018[C]. https://api.semanticscholar.org/CorpusID:90160574
[4] Lebedeva I S, Panikratova Y R, Sokolov O Y, et al. Effects of Sema on the Default Mode Network of the Brain[J]. Bulletin of Experimental Biology and Medicine, 2018,165(5):653-656.DOI:10.1007/s10517-018-4234-3.
[5] Stavchansky V V, Yuzhakov V V, Botsina A Y, et al. The effect of Sema and its C-end peptide PGP on the morphology and proliferative activity of rat brain cells during experimental ischemia: a pilot study[J]. Journal of Molecular Neuroscience, 2011,45(2):177-185.DOI:10.1007/s12031-010-9421-2.
[6] Timoshenko T V, Poletaeva I I, Pavlova G V, et al. Effect of neonatal injections of the neuropeptide Sema on cell proliferation in hippocampal dentate area in rats of two genotypes[J]. Dokl Biol Sci, 2009,424:78-80.DOI:10.1134/s0012496609010232.
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