The effect of intra-nasal co-treatment with insulin and growth factor-rich serum on behavioral defects, hippocampal oxidative-nitrosative stress, and histological changes induced by icv-STZ in a rat model

Naunyn-schmiedebergs Archives of Pharmacology Pub Date : 2023-12-29 DOI:10.1007/s00210-023-02899-3

{"title":"The effect of intra-nasal co-treatment with insulin and growth factor-rich serum on behavioral defects, hippocampal oxidative-nitrosative stress, and histological changes induced by icv-STZ in a rat model","authors":"","doi":"10.1007/s00210-023-02899-3","DOIUrl":null,"url":null,"abstract":"<h3>Abstract</h3> <p>Impaired insulin and growth factor functions are thought to drive many alterations in neurodegenerative diseases like dementia and seem to contribute to oxidative stress and inflammatory responses. Recent studies revealed that nasal growth factor therapy could induce neuronal and oligodendroglia protection in rodent brain damage induction models. Impairment of several growth factors signaling was reported in neurodegenerative diseases. So, in the present study, we examined the effects of intranasal co-treatment of insulin and a pool of growth factor-rich serum (GFRS) which separated from activated platelets on memory, and behavioral defects induced by intracerebroventricular streptozotocin (icv-STZ) rat model also investigated changes in the hippocampal oxidative-nitrosative state and histology. We found that icv-STZ injection (3 mg/kg bilaterally) impairs spatial learning and memory in Morris Water Maze, leads to anxiogenic-like behavior in the open field arena, and induces oxidative-nitrosative stress, neuroinflammation, and neuronal/oligodendroglia death in the hippocampus. GFRS (1µl/kg, each other day, 9 doses) and regular insulin (4 U/40 µl, daily, 18 doses) treatments improved learning, memory, and anxiogenic behaviors. The present study showed that co-treatment (GFRS + insulin with respective dose) has more robust protection against hippocampal oxidative-nitrosative stress, neuroinflammation, and neuronal/oligodendroglia survival in comparison with the single therapy. Memory and behavioral improvements in the co-treatment of insulin and GFRS could be attributed to their effects on neuronal/oligodendroglia survival and reduction of neuroinflammation in the hippocampus.</p> <span> <h3>Graphical Abstract</h3> <p> <span> <span> <img alt=\"\" src=\"https://static-content.springer.com/image/MediaObjects/210_2023_2899_Figa_HTML.png\"/> </span> </span></p> </span>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Naunyn-schmiedebergs Archives of Pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s00210-023-02899-3","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

Abstract

Impaired insulin and growth factor functions are thought to drive many alterations in neurodegenerative diseases like dementia and seem to contribute to oxidative stress and inflammatory responses. Recent studies revealed that nasal growth factor therapy could induce neuronal and oligodendroglia protection in rodent brain damage induction models. Impairment of several growth factors signaling was reported in neurodegenerative diseases. So, in the present study, we examined the effects of intranasal co-treatment of insulin and a pool of growth factor-rich serum (GFRS) which separated from activated platelets on memory, and behavioral defects induced by intracerebroventricular streptozotocin (icv-STZ) rat model also investigated changes in the hippocampal oxidative-nitrosative state and histology. We found that icv-STZ injection (3 mg/kg bilaterally) impairs spatial learning and memory in Morris Water Maze, leads to anxiogenic-like behavior in the open field arena, and induces oxidative-nitrosative stress, neuroinflammation, and neuronal/oligodendroglia death in the hippocampus. GFRS (1µl/kg, each other day, 9 doses) and regular insulin (4 U/40 µl, daily, 18 doses) treatments improved learning, memory, and anxiogenic behaviors. The present study showed that co-treatment (GFRS + insulin with respective dose) has more robust protection against hippocampal oxidative-nitrosative stress, neuroinflammation, and neuronal/oligodendroglia survival in comparison with the single therapy. Memory and behavioral improvements in the co-treatment of insulin and GFRS could be attributed to their effects on neuronal/oligodendroglia survival and reduction of neuroinflammation in the hippocampus.

Graphical Abstract

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

鼻腔内同时注射胰岛素和富含生长因子的血清对icv-STZ诱导的大鼠行为缺陷、海马氧化-亚硝基应激和组织学变化的影响

摘要胰岛素和生长因子功能受损被认为是痴呆症等神经退行性疾病发生许多变化的驱动因素，似乎也是氧化应激和炎症反应的促成因素。最近的研究表明，鼻腔生长因子疗法可在啮齿类脑损伤诱导模型中诱导神经元和少突胶质细胞保护。据报道，神经退行性疾病中存在多种生长因子信号传导障碍。因此，在本研究中，我们考察了胰岛素和从活化血小板中分离出的富含生长因子的血清池（GFRS）鼻内联合治疗对脑室注射链脲佐菌素（icv-STZ）诱导的大鼠模型记忆和行为缺陷的影响，并研究了海马氧化-亚硝基状态和组织学的变化。我们发现，注射icv-STZ（3 mg/kg，双侧）会损害莫里斯水迷宫（Morris Water Maze）的空间学习和记忆，导致开放场中的焦虑样行为，并诱导海马氧化亚硝酸盐应激、神经炎症和神经元/橄榄枝胶质细胞死亡。GFRS（1µl/kg，隔日1次，9次）和普通胰岛素（4 U/40µl，每日1次，18次）治疗可改善学习、记忆和焦虑行为。本研究表明，与单一疗法相比，联合疗法（GFRS + 胰岛素，各剂量）对海马氧化亚硝基应激、神经炎症和神经元/橄榄枝胶质细胞存活有更强的保护作用。胰岛素和GFRS联合治疗对记忆和行为的改善可能是由于它们对神经元/橄榄枝胶质细胞存活和减少海马神经炎症的作用。图表摘要

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Naunyn-schmiedebergs Archives of Pharmacology

自引率

0.00%

发文量