Seung H Jung, Laura K Olsen, Krysten A Jones, Raquel J Moore, Sean W Harshman, Candice N Hatcher-Solis
{"title":"VNS与训练配对增强识别记忆：来自海马突触蛋白质组学分析的机制见解。","authors":"Seung H Jung, Laura K Olsen, Krysten A Jones, Raquel J Moore, Sean W Harshman, Candice N Hatcher-Solis","doi":"10.3389/fnmol.2024.1452327","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Recognition memory, an essential component of cognitive health, can suffer from biological limitations of stress, aging, or neurodegenerative disease. Vagus nerve stimulation (VNS) is a neuromodulation therapy with the potential to improve cognitive function. This study investigated the effectiveness of multiple sessions of VNS to enhance recognition memory in healthy rodents and the underlying cognitive benefits of VNS by proteomic analysis of the synaptosome.</p><p><strong>Methods: </strong>Rats demonstrated VNS-induced recognition memory improvements using a novel object recognition (NOR) task. Using the LC-MS/MS method, roughly 3,000 proteins in the synaptosome of the hippocampus were analyzed.</p><p><strong>Results: </strong>Protein-protein interaction (PPI) enrichment analysis found differentially expressed proteins related to synaptic signaling and neurotransmitter pathways. PPI network analysis identified six unique protein clusters, including a cluster of synaptic signaling related pathways. Using ingenuity pathway analysis (IPA), rapamycin-insensitive companion of mTOR was identified as an upstream regulator of synaptosome changes due to VNS-paired training.</p><p><strong>Discussion: </strong>Based on these results, it is proposed that VNS may mediate cognitive enhancement via increases in glutamatergic signaling and early LTP during the consolidation period, followed by sustained synaptic plasticity via modified post-synaptic receptor expression and dendritic outgrowth. Further investigation is required to determine if VNS is a good candidate to ameliorate cognitive impairment.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"17 ","pages":"1452327"},"PeriodicalIF":3.5000,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685747/pdf/","citationCount":"0","resultStr":"{\"title\":\"VNS paired with training enhances recognition memory: mechanistic insights from proteomic analysis of the hippocampal synapse.\",\"authors\":\"Seung H Jung, Laura K Olsen, Krysten A Jones, Raquel J Moore, Sean W Harshman, Candice N Hatcher-Solis\",\"doi\":\"10.3389/fnmol.2024.1452327\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Recognition memory, an essential component of cognitive health, can suffer from biological limitations of stress, aging, or neurodegenerative disease. Vagus nerve stimulation (VNS) is a neuromodulation therapy with the potential to improve cognitive function. This study investigated the effectiveness of multiple sessions of VNS to enhance recognition memory in healthy rodents and the underlying cognitive benefits of VNS by proteomic analysis of the synaptosome.</p><p><strong>Methods: </strong>Rats demonstrated VNS-induced recognition memory improvements using a novel object recognition (NOR) task. Using the LC-MS/MS method, roughly 3,000 proteins in the synaptosome of the hippocampus were analyzed.</p><p><strong>Results: </strong>Protein-protein interaction (PPI) enrichment analysis found differentially expressed proteins related to synaptic signaling and neurotransmitter pathways. PPI network analysis identified six unique protein clusters, including a cluster of synaptic signaling related pathways. Using ingenuity pathway analysis (IPA), rapamycin-insensitive companion of mTOR was identified as an upstream regulator of synaptosome changes due to VNS-paired training.</p><p><strong>Discussion: </strong>Based on these results, it is proposed that VNS may mediate cognitive enhancement via increases in glutamatergic signaling and early LTP during the consolidation period, followed by sustained synaptic plasticity via modified post-synaptic receptor expression and dendritic outgrowth. Further investigation is required to determine if VNS is a good candidate to ameliorate cognitive impairment.</p>\",\"PeriodicalId\":12630,\"journal\":{\"name\":\"Frontiers in Molecular Neuroscience\",\"volume\":\"17 \",\"pages\":\"1452327\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-12-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685747/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Molecular Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fnmol.2024.1452327\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Molecular Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fnmol.2024.1452327","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
VNS paired with training enhances recognition memory: mechanistic insights from proteomic analysis of the hippocampal synapse.
Introduction: Recognition memory, an essential component of cognitive health, can suffer from biological limitations of stress, aging, or neurodegenerative disease. Vagus nerve stimulation (VNS) is a neuromodulation therapy with the potential to improve cognitive function. This study investigated the effectiveness of multiple sessions of VNS to enhance recognition memory in healthy rodents and the underlying cognitive benefits of VNS by proteomic analysis of the synaptosome.
Methods: Rats demonstrated VNS-induced recognition memory improvements using a novel object recognition (NOR) task. Using the LC-MS/MS method, roughly 3,000 proteins in the synaptosome of the hippocampus were analyzed.
Results: Protein-protein interaction (PPI) enrichment analysis found differentially expressed proteins related to synaptic signaling and neurotransmitter pathways. PPI network analysis identified six unique protein clusters, including a cluster of synaptic signaling related pathways. Using ingenuity pathway analysis (IPA), rapamycin-insensitive companion of mTOR was identified as an upstream regulator of synaptosome changes due to VNS-paired training.
Discussion: Based on these results, it is proposed that VNS may mediate cognitive enhancement via increases in glutamatergic signaling and early LTP during the consolidation period, followed by sustained synaptic plasticity via modified post-synaptic receptor expression and dendritic outgrowth. Further investigation is required to determine if VNS is a good candidate to ameliorate cognitive impairment.
期刊介绍：
Frontiers in Molecular Neuroscience is a first-tier electronic journal devoted to identifying key molecules, as well as their functions and interactions, that underlie the structure, design and function of the brain across all levels. The scope of our journal encompasses synaptic and cellular proteins, coding and non-coding RNA, and molecular mechanisms regulating cellular and dendritic RNA translation. In recent years, a plethora of new cellular and synaptic players have been identified from reduced systems, such as neuronal cultures, but the relevance of these molecules in terms of cellular and synaptic function and plasticity in the living brain and its circuits has not been validated. The effects of spine growth and density observed using gene products identified from in vitro work are frequently not reproduced in vivo. Our journal is particularly interested in studies on genetically engineered model organisms (C. elegans, Drosophila, mouse), in which alterations in key molecules underlying cellular and synaptic function and plasticity produce defined anatomical, physiological and behavioral changes. In the mouse, genetic alterations limited to particular neural circuits (olfactory bulb, motor cortex, cortical layers, hippocampal subfields, cerebellum), preferably regulated in time and on demand, are of special interest, as they sidestep potential compensatory developmental effects.
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