星形胶质细胞对丙戊酸诱导自闭症动物模型中内源性和纳米促红细胞生成素治疗的反应。
Astrocyte responses to postnatal erythropoietin and nano-erythropoietin treatments in a valproic acid-induced animal model of autism.
机构信息
Student Research Committee, Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Islamic Republic of Iran.
Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Islamic Republic of Iran.
出版信息
J Chem Neuroanat. 2023 Jul;130:102257. doi: 10.1016/j.jchemneu.2023.102257. Epub 2023 Mar 13.
BACKGROUND
Despite ample evidence of the potential protective effects of erythropoietin (EPO) on the developing brain, no study has addressed the effects of postnatal EPO on behaviors and brain tissue of animal models of autism. In the present study, we examined the therapeutic effects of postnatal erythropoietin on stereotypic behaviors and astrocyte responses via glial fibrillary acidic protein (GFAP) and S100 calcium-binding protein B (S100B) immunohistochemistry in a valproic acid (VPA) animal model of autism. Also, we compared the effects of EPO with EPO-loaded solid lipid nanoparticles (NEPO) because the blood-brain barrier has limited permeability to EPO.
METHODS
Pregnant rats received a single dose of VPA (600 mg/kg) at gestational day 12.5. EPO (2000 U/kg) and EPO-loaded solid lipid nanoparticles (NEPO1000 and 2000 U/kg) were injected intraperitoneally from postnatal days 1-5. Repetitive behaviors in male offspring were assessed by a marble burying test. The immune-staining method was performed to evaluate S100B and GFAP-positive cells in the prefrontal cortex and hippocampal CA1 region.
RESULTS
VPA animal models revealed more repetitive behavior and displayed higher astrogliosis in the prefrontal cortex (PFC) and hippocampus (CA1) regions. The repetitive behaviors were ameliorated relatively in VPA groups with NEPO2000 treatment, and astrogliosis was reduced even when VPA rats were treated with a lower dosage of NEPO.
CONCLUSION
Our results indicate beneficial effects of postnatal NEPO exposure in the VPA animal model of autism, which proposes it as an early treatment in infants with, or at risk of, autism.
背景
尽管有大量证据表明促红细胞生成素（EPO）对发育中的大脑有潜在的保护作用，但没有研究探讨过 EPO 对自闭症动物模型的行为和脑组织的影响。在本研究中，我们通过胶质纤维酸性蛋白（GFAP）和 S100 钙结合蛋白 B（S100B）免疫组织化学检测，研究了产后 EPO 对自闭症动物模型刻板行为和星形胶质细胞反应的治疗作用。此外，我们比较了 EPO 和载 EPO 的固体脂质纳米粒（NEPO）的作用，因为血脑屏障对 EPO 的通透性有限。
方法
妊娠大鼠在妊娠第 12.5 天接受单次 VPA（600mg/kg）注射。EPO（2000U/kg）和载 EPO 的固体脂质纳米粒（NEPO1000 和 2000U/kg）于产后第 1-5 天腹腔内注射。雄性幼鼠的重复性行为通过埋珠试验进行评估。免疫染色法用于评估前额叶皮质和海马 CA1 区的 S100B 和 GFAP 阳性细胞。
结果
VPA 动物模型表现出更多的重复性行为，并显示前额叶皮质（PFC）和海马（CA1）区域的星形胶质细胞增生增加。NEPO2000 治疗可使 VPA 组的重复性行为得到改善，即使 VPA 大鼠接受较低剂量的 NEPO 治疗，星形胶质细胞增生也会减少。
结论
我们的结果表明，产后 NEPO 暴露对自闭症 VPA 动物模型具有有益作用，这表明它可作为自闭症患儿或有自闭症风险的婴儿的早期治疗方法。
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