Mümin Alper Erdoğan, Kerem Can Tunç, Ali İmran Daştan, Canberk Tomruk, Yiğit Uyanıkgil, Oytun Erbaş
{"title":"喷托塞林对丙酸诱发的大鼠自闭症症状的治疗作用：行为、生化和组织病理学研究","authors":"Mümin Alper Erdoğan, Kerem Can Tunç, Ali İmran Daştan, Canberk Tomruk, Yiğit Uyanıkgil, Oytun Erbaş","doi":"10.1002/jdn.10394","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>The role of propionic acid (PPA) in eliciting behaviors analogous to autism in rat models is a documented phenomenon. This study examines the therapeutic implications of pentoxifylline—an agent traditionally used for peripheral vascular diseases—on these autism-like behaviors by modulating brain proteins and reducing pro-inflammatory cytokines like tumor necrosis factor-α (TNF-α) in a rat model.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>This research involved 30 male <i>Wistar albino</i> rats, which were divided into three distinct groups: a baseline control set, a PPA-treated cluster receiving a 250 mg/kg/day dose of PPA via intraperitoneal injection for a span of five days followed by saline orally, and a PPA group administered an oral dose of pentoxifylline at 300 mg/kg/day over 15 days. Subsequent to the treatment phase, euthanasia was carried out for the extraction of brain and blood samples, which were then analyzed for histopathological and biochemical markers.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The pentoxifylline-treated subjects demonstrated a significant mitigation in the manifestation of autistic-like behaviors, as assessed through a triad of social interaction tests. A noteworthy decline in TNF-α levels was observed, alongside a significant rise in the concentration of adenosine triphosphate and nerve growth factor in brain tissue (p < 0.05). Histopathological analysis underscored a reduction in oxidative stress and a significant preservation of neuronal cell types, specifically pyramidal neurons in the hippocampal CA1 and CA3 regions and Purkinje cells in the cerebellum (p < 0.001).</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Pentoxifylline treatment has been found to effectively reduce the behavioral symptoms associated with autism, as well as biochemical and histopathological disruptions induced by PPA in rat models, highlighting its potential as a neurotherapeutic agent.</p>\n </section>\n </div>","PeriodicalId":13914,"journal":{"name":"International Journal of Developmental Neuroscience","volume":"84 8","pages":"991-1005"},"PeriodicalIF":1.7000,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Therapeutic effects of pentoxifylline in propionic acid-induced autism symptoms in rat models: A behavioral, biochemical, and histopathological study\",\"authors\":\"Mümin Alper Erdoğan, Kerem Can Tunç, Ali İmran Daştan, Canberk Tomruk, Yiğit Uyanıkgil, Oytun Erbaş\",\"doi\":\"10.1002/jdn.10394\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>The role of propionic acid (PPA) in eliciting behaviors analogous to autism in rat models is a documented phenomenon. This study examines the therapeutic implications of pentoxifylline—an agent traditionally used for peripheral vascular diseases—on these autism-like behaviors by modulating brain proteins and reducing pro-inflammatory cytokines like tumor necrosis factor-α (TNF-α) in a rat model.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>This research involved 30 male <i>Wistar albino</i> rats, which were divided into three distinct groups: a baseline control set, a PPA-treated cluster receiving a 250 mg/kg/day dose of PPA via intraperitoneal injection for a span of five days followed by saline orally, and a PPA group administered an oral dose of pentoxifylline at 300 mg/kg/day over 15 days. Subsequent to the treatment phase, euthanasia was carried out for the extraction of brain and blood samples, which were then analyzed for histopathological and biochemical markers.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>The pentoxifylline-treated subjects demonstrated a significant mitigation in the manifestation of autistic-like behaviors, as assessed through a triad of social interaction tests. A noteworthy decline in TNF-α levels was observed, alongside a significant rise in the concentration of adenosine triphosphate and nerve growth factor in brain tissue (p < 0.05). Histopathological analysis underscored a reduction in oxidative stress and a significant preservation of neuronal cell types, specifically pyramidal neurons in the hippocampal CA1 and CA3 regions and Purkinje cells in the cerebellum (p < 0.001).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>Pentoxifylline treatment has been found to effectively reduce the behavioral symptoms associated with autism, as well as biochemical and histopathological disruptions induced by PPA in rat models, highlighting its potential as a neurotherapeutic agent.</p>\\n </section>\\n </div>\",\"PeriodicalId\":13914,\"journal\":{\"name\":\"International Journal of Developmental Neuroscience\",\"volume\":\"84 8\",\"pages\":\"991-1005\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-11-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Developmental Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jdn.10394\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"DEVELOPMENTAL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Developmental Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jdn.10394","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}
Therapeutic effects of pentoxifylline in propionic acid-induced autism symptoms in rat models: A behavioral, biochemical, and histopathological study
Objective
The role of propionic acid (PPA) in eliciting behaviors analogous to autism in rat models is a documented phenomenon. This study examines the therapeutic implications of pentoxifylline—an agent traditionally used for peripheral vascular diseases—on these autism-like behaviors by modulating brain proteins and reducing pro-inflammatory cytokines like tumor necrosis factor-α (TNF-α) in a rat model.
Methods
This research involved 30 male Wistar albino rats, which were divided into three distinct groups: a baseline control set, a PPA-treated cluster receiving a 250 mg/kg/day dose of PPA via intraperitoneal injection for a span of five days followed by saline orally, and a PPA group administered an oral dose of pentoxifylline at 300 mg/kg/day over 15 days. Subsequent to the treatment phase, euthanasia was carried out for the extraction of brain and blood samples, which were then analyzed for histopathological and biochemical markers.
Results
The pentoxifylline-treated subjects demonstrated a significant mitigation in the manifestation of autistic-like behaviors, as assessed through a triad of social interaction tests. A noteworthy decline in TNF-α levels was observed, alongside a significant rise in the concentration of adenosine triphosphate and nerve growth factor in brain tissue (p < 0.05). Histopathological analysis underscored a reduction in oxidative stress and a significant preservation of neuronal cell types, specifically pyramidal neurons in the hippocampal CA1 and CA3 regions and Purkinje cells in the cerebellum (p < 0.001).
Conclusion
Pentoxifylline treatment has been found to effectively reduce the behavioral symptoms associated with autism, as well as biochemical and histopathological disruptions induced by PPA in rat models, highlighting its potential as a neurotherapeutic agent.
期刊介绍：
International Journal of Developmental Neuroscience publishes original research articles and critical review papers on all fundamental and clinical aspects of nervous system development, renewal and regeneration, as well as on the effects of genetic and environmental perturbations of brain development and homeostasis leading to neurodevelopmental disorders and neurological conditions. Studies describing the involvement of stem cells in nervous system maintenance and disease (including brain tumours), stem cell-based approaches for the investigation of neurodegenerative diseases, roles of neuroinflammation in development and disease, and neuroevolution are also encouraged. Investigations using molecular, cellular, physiological, genetic and epigenetic approaches in model systems ranging from simple invertebrates to human iPSC-based 2D and 3D models are encouraged, as are studies using experimental models that provide behavioural or evolutionary insights. The journal also publishes Special Issues dealing with topics at the cutting edge of research edited by Guest Editors appointed by the Editor in Chief. A major aim of the journal is to facilitate the transfer of fundamental studies of nervous system development, maintenance, and disease to clinical applications. The journal thus intends to disseminate valuable information for both biologists and physicians. International Journal of Developmental Neuroscience is owned and supported by The International Society for Developmental Neuroscience (ISDN), an organization of scientists interested in advancing developmental neuroscience research in the broadest sense.
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