Andrea Riberas-Sánchez, Irene Puig-Parnau, Laia Vila-Solés, Soleil Garcia-Brito, Laura Aldavert-Vera, Pilar Segura-Torres, Gemma Huguet, Elisabet Kádár
{"title":"颅内自我刺激可逆转链脲佐菌素诱导的阿尔茨海默病大鼠模型中受损的空间学习能力，并调节血清微RNA水平。","authors":"Andrea Riberas-Sánchez, Irene Puig-Parnau, Laia Vila-Solés, Soleil Garcia-Brito, Laura Aldavert-Vera, Pilar Segura-Torres, Gemma Huguet, Elisabet Kádár","doi":"10.1503/jpn.230066","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The assessment of deep brain stimulation (DBS) as a therapeutic alternative for treating Alzheimer disease (AD) is ongoing. We aimed to determine the effects of intracranial self-stimulation at the medial forebrain bundle (MFB-ICSS) on spatial memory, neurodegeneration, and serum expression of microRNAs (miRNAs) in a rat model of sporadic AD created by injection of streptozotocin. We hypothesized that MFB-ICSS would reverse the behavioural effects of streptozotocin and modulate hippocampal neuronal density and serum levels of the miRNAs.</p><p><strong>Methods: </strong>We performed Morris water maze and light-dark transition tests. Levels of various proteins, specifically amyloid-β precurser protein (APP), phosphorylated tau protein (pTAU), and sirtuin 1 (SIRT1), and neurodegeneration were analyzed by Western blot and Nissl staining, respectively. Serum miRNA expression was measured by reverse transcription polymerase chain reaction.</p><p><strong>Results: </strong>Male rats that received streptozotocin had increased hippocampal levels of pTAU S202/T205, APP, and SIRT1 proteins; increased neurodegeneration in the CA1, dentate gyrus (DG), and dorsal tenia tecta; and worse performance in the Morris water maze task. No differences were observed in miRNAs, except for miR-181c and miR-let-7b. After MFB-ICSS, neuronal density in the CA1 and DG regions and levels of miR-181c in streptozotocin-treated and control rats were similar. Rats that received streptozotocin and underwent MFB-ICSS also showed lower levels of miR-let-7b and better spatial learning than rats that received streptozotocin without MFB-ICSS.</p><p><strong>Limitations: </strong>The reversal by MFB-ICSS of deficits induced by streptozotocin was fairly modest.</p><p><strong>Conclusion: </strong>Spatial memory performance, hippocampal neurodegeneration, and serum levels of miR-let-7b and miR-181c were affected by MFB-ICSS under AD-like conditions. Our results validate the MFB as a potential target for DBS and lend support to the use of specific miRNAs as promising biomarkers of the effectiveness of DBS in combatting AD-associated cognitive deficits.</p>","PeriodicalId":50073,"journal":{"name":"Journal of Psychiatry & Neuroscience","volume":"49 2","pages":"E96-E108"},"PeriodicalIF":4.1000,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10950362/pdf/","citationCount":"0","resultStr":"{\"title\":\"Intracranial self-stimulation reverses impaired spatial learning and regulates serum microRNA levels in a streptozotocin-induced rat model of Alzheimer disease.\",\"authors\":\"Andrea Riberas-Sánchez, Irene Puig-Parnau, Laia Vila-Solés, Soleil Garcia-Brito, Laura Aldavert-Vera, Pilar Segura-Torres, Gemma Huguet, Elisabet Kádár\",\"doi\":\"10.1503/jpn.230066\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The assessment of deep brain stimulation (DBS) as a therapeutic alternative for treating Alzheimer disease (AD) is ongoing. We aimed to determine the effects of intracranial self-stimulation at the medial forebrain bundle (MFB-ICSS) on spatial memory, neurodegeneration, and serum expression of microRNAs (miRNAs) in a rat model of sporadic AD created by injection of streptozotocin. We hypothesized that MFB-ICSS would reverse the behavioural effects of streptozotocin and modulate hippocampal neuronal density and serum levels of the miRNAs.</p><p><strong>Methods: </strong>We performed Morris water maze and light-dark transition tests. Levels of various proteins, specifically amyloid-β precurser protein (APP), phosphorylated tau protein (pTAU), and sirtuin 1 (SIRT1), and neurodegeneration were analyzed by Western blot and Nissl staining, respectively. Serum miRNA expression was measured by reverse transcription polymerase chain reaction.</p><p><strong>Results: </strong>Male rats that received streptozotocin had increased hippocampal levels of pTAU S202/T205, APP, and SIRT1 proteins; increased neurodegeneration in the CA1, dentate gyrus (DG), and dorsal tenia tecta; and worse performance in the Morris water maze task. No differences were observed in miRNAs, except for miR-181c and miR-let-7b. After MFB-ICSS, neuronal density in the CA1 and DG regions and levels of miR-181c in streptozotocin-treated and control rats were similar. Rats that received streptozotocin and underwent MFB-ICSS also showed lower levels of miR-let-7b and better spatial learning than rats that received streptozotocin without MFB-ICSS.</p><p><strong>Limitations: </strong>The reversal by MFB-ICSS of deficits induced by streptozotocin was fairly modest.</p><p><strong>Conclusion: </strong>Spatial memory performance, hippocampal neurodegeneration, and serum levels of miR-let-7b and miR-181c were affected by MFB-ICSS under AD-like conditions. Our results validate the MFB as a potential target for DBS and lend support to the use of specific miRNAs as promising biomarkers of the effectiveness of DBS in combatting AD-associated cognitive deficits.</p>\",\"PeriodicalId\":50073,\"journal\":{\"name\":\"Journal of Psychiatry & Neuroscience\",\"volume\":\"49 2\",\"pages\":\"E96-E108\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2024-03-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10950362/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Psychiatry & Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1503/jpn.230066\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"Print\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Psychiatry & Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1503/jpn.230066","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"Print","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Intracranial self-stimulation reverses impaired spatial learning and regulates serum microRNA levels in a streptozotocin-induced rat model of Alzheimer disease.
Background: The assessment of deep brain stimulation (DBS) as a therapeutic alternative for treating Alzheimer disease (AD) is ongoing. We aimed to determine the effects of intracranial self-stimulation at the medial forebrain bundle (MFB-ICSS) on spatial memory, neurodegeneration, and serum expression of microRNAs (miRNAs) in a rat model of sporadic AD created by injection of streptozotocin. We hypothesized that MFB-ICSS would reverse the behavioural effects of streptozotocin and modulate hippocampal neuronal density and serum levels of the miRNAs.
Methods: We performed Morris water maze and light-dark transition tests. Levels of various proteins, specifically amyloid-β precurser protein (APP), phosphorylated tau protein (pTAU), and sirtuin 1 (SIRT1), and neurodegeneration were analyzed by Western blot and Nissl staining, respectively. Serum miRNA expression was measured by reverse transcription polymerase chain reaction.
Results: Male rats that received streptozotocin had increased hippocampal levels of pTAU S202/T205, APP, and SIRT1 proteins; increased neurodegeneration in the CA1, dentate gyrus (DG), and dorsal tenia tecta; and worse performance in the Morris water maze task. No differences were observed in miRNAs, except for miR-181c and miR-let-7b. After MFB-ICSS, neuronal density in the CA1 and DG regions and levels of miR-181c in streptozotocin-treated and control rats were similar. Rats that received streptozotocin and underwent MFB-ICSS also showed lower levels of miR-let-7b and better spatial learning than rats that received streptozotocin without MFB-ICSS.
Limitations: The reversal by MFB-ICSS of deficits induced by streptozotocin was fairly modest.
Conclusion: Spatial memory performance, hippocampal neurodegeneration, and serum levels of miR-let-7b and miR-181c were affected by MFB-ICSS under AD-like conditions. Our results validate the MFB as a potential target for DBS and lend support to the use of specific miRNAs as promising biomarkers of the effectiveness of DBS in combatting AD-associated cognitive deficits.
期刊介绍：
The Journal of Psychiatry & Neuroscience publishes papers at the intersection of psychiatry and neuroscience that advance our understanding of the neural mechanisms involved in the etiology and treatment of psychiatric disorders. This includes studies on patients with psychiatric disorders, healthy humans, and experimental animals as well as studies in vitro. Original research articles, including clinical trials with a mechanistic component, and review papers will be considered.
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