Tunç Erdinç, Aygün Hatice, Erdoğan Mümin Alper, Uyanıkgil Yiğit, Erbaş Oytun
Department of Anatomy, Faculty of Medicine, Biruni University, 34295 Istanbul, Türkiye.
Department of Physiology, Faculty of Medicine, Tokat Gaziosmanpaşa University, 60030 Tokat, Türkiye.
Int J Mol Sci. 2025 May 30;26(11):5285. doi: 10.3390/ijms26115285.
Radiation exposure causes neuroinflammation, oxidative stress, and neuronal loss, leading to cognitive and behavioral impairments. This study aims to evaluate the effect of niacin interventions on whole-brain irradiation (WBI)-induced cognitive and behavioral impairment. Female Wistar rats were randomly assigned to Control (Group 1), Radiation +Saline (Group 2), and Radiation +niacin (Group 3) groups. Rats in the irradiated groups (Groups 2 and 3) received a single dose of 20 Gy photon irradiation. Group 2 received water seven days after irradiation, while Group 3 received niacin (60 mg/kg, 2 mL) oral gavage for 15 days. On days 22, 23, and 24, behavioral assessments were performed, including the Open Field Test, the Sociability Test, and the Passive Avoidance Learning (PAL) task. Biochemical analyses included MDA, BDNF, TNF-α, CREB), SIRT1, and SIRT6 measured by ELISA. Histological assessments included neuronal density and GFAP immunostaining in CA1 and CA3 regions of the hippocampus and cerebellar Purkinje neurons. Radiation exposure importantly increased MDA and TNF-α levels, while SIRT1, SIRT6, BDNF, and CREB were notably reduced. This was accompanied by neuronal loss in the cerebellum and hippocampus, astrogliosis, and behavioral and cognitive deficits. Niacin treatment significantly decreased MDA and TNF-α levels while increasing BDNF, CREB, SIRT1, and SIRT6 expression, attenuating neuronal apoptosis. Immunohistochemical analysis demonstrated that niacin treatment enhanced neuronal density in the CA1 and CA3 regions of the hippocampus and cerebellar Purkinje neurons while reducing GFAP immunoreactivity in the CA1, CA3, and cerebellum following WBI. Behaviorally, niacin treatment improved social interaction, locomotor activity, and memory performance, underscoring its neuroprotective potential against WBI-induced damage. These findings suggest that niacin may ameliorate behavioral and cognitive impairments following whole brain irradiation by activating the SIRT1/CREB/BDNF or SIRT1/SIRT6/MDA/TNF-α signaling pathway.
辐射暴露会引发神经炎症、氧化应激和神经元丢失，导致认知和行为障碍。本研究旨在评估烟酸干预对全脑照射（WBI）诱导的认知和行为障碍的影响。将雌性Wistar大鼠随机分为对照组（第1组）、辐射+生理盐水组（第2组）和辐射+烟酸组（第3组）。照射组（第2组和第3组）的大鼠接受单次20 Gy光子照射。第2组在照射后7天给予水，而第3组接受烟酸（60 mg/kg，2 mL）灌胃15天。在第22、23和24天进行行为评估，包括旷场试验、社交能力试验和被动回避学习（PAL）任务。生化分析包括通过酶联免疫吸附测定法测量丙二醛（MDA）、脑源性神经营养因子（BDNF）、肿瘤坏死因子-α（TNF-α）、环磷腺苷效应元件结合蛋白（CREB）、沉默信息调节因子1（SIRT1）和沉默信息调节因子6（SIRT6）。组织学评估包括海马CA1和CA3区域以及小脑浦肯野神经元的神经元密度和胶质纤维酸性蛋白（GFAP）免疫染色。辐射暴露显著增加了MDA和TNF-α水平，而SIRT1、SIRT6、BDNF和CREB明显降低。这伴随着小脑和海马中的神经元丢失、星形胶质细胞增生以及行为和认知缺陷。烟酸治疗显著降低了MDA和TNF-α水平，同时增加了BDNF、CREB、SIRT1和SIRT6的表达，减轻了神经元凋亡。免疫组织化学分析表明，烟酸治疗增加了海马CA1和CA3区域以及小脑浦肯野神经元的神经元密度，同时降低了WBI后CA1、CA3和小脑中的GFAP免疫反应性。在行为方面，烟酸治疗改善了社交互动、运动活动和记忆表现，突出了其对WBI诱导损伤的神经保护潜力。这些发现表明，烟酸可能通过激活SIRT1/CREB/BDNF或SIRT1/SIRT6/MDA/TNF-α信号通路改善全脑照射后的行为和认知障碍。
