Nóra Bruszt, Zsolt Kristóf Bali, Lili Veronika Nagy, Kornélia Bodó, Péter Engelmann, István Hernádi
{"title":"美金刚与α - 7烟碱乙酰胆碱受体激动剂PHA-543613对老年大鼠记忆力的协同作用。","authors":"Nóra Bruszt, Zsolt Kristóf Bali, Lili Veronika Nagy, Kornélia Bodó, Péter Engelmann, István Hernádi","doi":"10.1093/ijnp/pyaf014","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Combination treatments based on pharmacological interactions at α7 nicotinic acetylcholine receptors (nAChRs) are promising therapeutic approaches for neurocognitive disorders.</p><p><strong>Methods: </strong>Here, we tested the cognitive efficacy of combinations of memantine with an α7 nAChR-selective agonist (PHA-543613) in naturally aged rats. Age-related changes in the expression of some key genes and proteins were also measured using quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>Aged rats showed marked cognitive decline in the novel object recognition test, and they also exhibited cholinergic changes such as mRNA upregulation of α7 nAChRs. Upregulation of interleukin-1β, macrophage inflammatory protein 1α, CX3CL1, intercellular adhesion molecule 1, and ciliary neurotrophic factor mRNA was also detected in aged rats. Combination treatment of memantine and PHA-543613 successfully alleviated the age-related decline of recognition memory of rats by exceeding the effects of the corresponding monotreatments.</p><p><strong>Conclusions: </strong>Results indicate a positive interaction between memantine and PHA-543613, which also reflects a putative role of α7 nAChRs in the cognitive enhancer effects of memantine. These findings may facilitate the development of combination therapies for age-related neurocognitive disorders.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929953/pdf/","citationCount":"0","resultStr":"{\"title\":\"Synergistic effects of memantine and alpha7 nicotinic acetylcholine receptor agonist PHA-543613 to improve memory of aged rats.\",\"authors\":\"Nóra Bruszt, Zsolt Kristóf Bali, Lili Veronika Nagy, Kornélia Bodó, Péter Engelmann, István Hernádi\",\"doi\":\"10.1093/ijnp/pyaf014\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Combination treatments based on pharmacological interactions at α7 nicotinic acetylcholine receptors (nAChRs) are promising therapeutic approaches for neurocognitive disorders.</p><p><strong>Methods: </strong>Here, we tested the cognitive efficacy of combinations of memantine with an α7 nAChR-selective agonist (PHA-543613) in naturally aged rats. Age-related changes in the expression of some key genes and proteins were also measured using quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>Aged rats showed marked cognitive decline in the novel object recognition test, and they also exhibited cholinergic changes such as mRNA upregulation of α7 nAChRs. Upregulation of interleukin-1β, macrophage inflammatory protein 1α, CX3CL1, intercellular adhesion molecule 1, and ciliary neurotrophic factor mRNA was also detected in aged rats. Combination treatment of memantine and PHA-543613 successfully alleviated the age-related decline of recognition memory of rats by exceeding the effects of the corresponding monotreatments.</p><p><strong>Conclusions: </strong>Results indicate a positive interaction between memantine and PHA-543613, which also reflects a putative role of α7 nAChRs in the cognitive enhancer effects of memantine. 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Synergistic effects of memantine and alpha7 nicotinic acetylcholine receptor agonist PHA-543613 to improve memory of aged rats.
Background: Combination treatments based on pharmacological interactions at α7 nicotinic acetylcholine receptors (nAChRs) are promising therapeutic approaches for neurocognitive disorders.
Methods: Here, we tested the cognitive efficacy of combinations of memantine with an α7 nAChR-selective agonist (PHA-543613) in naturally aged rats. Age-related changes in the expression of some key genes and proteins were also measured using quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA).
Results: Aged rats showed marked cognitive decline in the novel object recognition test, and they also exhibited cholinergic changes such as mRNA upregulation of α7 nAChRs. Upregulation of interleukin-1β, macrophage inflammatory protein 1α, CX3CL1, intercellular adhesion molecule 1, and ciliary neurotrophic factor mRNA was also detected in aged rats. Combination treatment of memantine and PHA-543613 successfully alleviated the age-related decline of recognition memory of rats by exceeding the effects of the corresponding monotreatments.
Conclusions: Results indicate a positive interaction between memantine and PHA-543613, which also reflects a putative role of α7 nAChRs in the cognitive enhancer effects of memantine. These findings may facilitate the development of combination therapies for age-related neurocognitive disorders.
期刊介绍：
The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.
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