Arda Duygu Burcu, Tunç Kerem Can, Bozkurt Mehmet Fatih, Bora Ejder Saylav, Çiğel Ayşe, Erbaş Oytun
Department of Pediatrics, Taksim Research and Training Hospital, Istanbul 34365, Türkiye.
Department of Biology, Faculty of Science, Adnan Menderes University, Aydın 09010, Türkiye.
Curr Issues Mol Biol. 2024 Sep 20;46(9):10530-10544. doi: 10.3390/cimb46090624.
In rat models, it is well-documented that chronic administration of propionic acid (PPA) leads to autism-like behaviors. Although the intranasal (IN) insulin approach is predominantly recognized for its effects on food restriction, it has also been shown to enhance cognitive memory by influencing various proteins, modulating anti-inflammatory pathways in the brain, and reducing signaling molecules such as interleukins. This study seeks to explore the potential therapeutic benefits of IN insulin in a rat model of autism induced by PPA. Thirty male Wistar albino rats were categorized into three cohorts: the control group, the PPA-induced autism (250 mg/kg/day intraperitoneal PPA dosage for five days) group, treated with saline via IN, and the PPA-induced autism group, treated with 25 U/kg/day (250 µL/kg/day) insulin via IN. All treatments were administered for 15 days. After behavioral testing, all animals were euthanized, and brain tissue and blood samples were collected for histopathological and biochemical assessments. Following insulin administration, a substantial reduction in autism symptoms was observed in all three social behavior tests conducted on the rats. Moreover, insulin exhibited noteworthy capabilities in decreasing brain MDA, IL-2, IL-17, and TNF-α levels within autism models. Additionally, there is a notable elevation in the brain nerve growth factor level ( < 0.05) and GDF-15 ( < 0.05). The assessment of cell counts within the hippocampal region and cerebellum revealed that insulin displayed effects in decreasing glial cells and inducing a significant augmentation in cell types such as the Purkinje and Pyramidal cells. The administration of insulin via IN exhibits alleviating effects on autism-like behavioral, biochemical, and histopathological alterations induced by PPA in rats. Insulin-dependent protective effects show anti-inflammatory, anti-oxidative, and neuroprotective roles of insulin admitted nasally.
在大鼠模型中，有充分的文献记载，长期给予丙酸（PPA）会导致自闭症样行为。尽管鼻内（IN）胰岛素疗法主要因其对食物限制的作用而被认可，但它也已被证明可通过影响各种蛋白质、调节大脑中的抗炎途径以及减少白细胞介素等信号分子来增强认知记忆。本研究旨在探讨IN胰岛素在PPA诱导的大鼠自闭症模型中的潜在治疗益处。30只雄性Wistar白化大鼠被分为三组：对照组、PPA诱导的自闭症组（腹腔注射PPA剂量为250 mg/kg/天，持续五天），经鼻给予生理盐水，以及PPA诱导的自闭症组，经鼻给予25 U/kg/天（250 μL/kg/天）胰岛素。所有治疗均持续15天。行为测试后，对所有动物实施安乐死，并采集脑组织和血液样本进行组织病理学和生化评估。给予胰岛素后，在对大鼠进行的所有三项社交行为测试中，自闭症症状均有显著减轻。此外，胰岛素在自闭症模型中具有显著降低脑内丙二醛、白细胞介素-2、白细胞介素-17和肿瘤坏死因子-α水平的能力。此外，脑神经营养因子水平（<0.05）和生长分化因子-15（<0.05）有显著升高。对海马区和小脑内细胞计数的评估显示，胰岛素具有减少胶质细胞并使浦肯野细胞和锥体细胞等细胞类型显著增加的作用。经鼻给予胰岛素对PPA诱导的大鼠自闭症样行为、生化和组织病理学改变具有缓解作用。胰岛素依赖性保护作用显示了经鼻给予胰岛素的抗炎、抗氧化和神经保护作用。
