Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital/Center, No. 519 Kunzhou Road, Xishan District, Kunming 650118, Yunnan, PR China.
Department of Second Urology, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Kunming 650032, Yunnan, PR China.
Neurotoxicology. 2022 Jul;91:119-127. doi: 10.1016/j.neuro.2022.05.005. Epub 2022 May 14.
The aim of this study was to evaluate the effect of radiation-induced brain injury (RIBI) on axonal transport (AT) and sexual function.
Adult male rats received whole-brain radiation with a total dose of 30 Gy (15 Gy with 2 fractions) to build a RIBI model. Foraging behavior and sexual function were assessed, and MRI was performed 8 weeks after brain irradiation. MRI was performed in the early and delayed phases after perfusion of MnCl into the rat nostril. The levels of motor proteins and proteins involved in energy metabolism and AT were determined by Western blotting. The levels of sex hormones in the blood were measured by ELISA. Ultrastructural analysis was performed with a transmission electron microscope.
The foraging ability of rats was reduced after brain irradiation, and the foraging time of the radiation group was longer than that of the control group (P < 0.05). The sexual function of rats in the radiation group was markedly decreased. Compared with control rats, radiation-treated rats showed significant decreases in serum testosterone, FSH, LH, and GnRH levels (P < 0.001). Mn uptake in the olfactory bulb (OB) in the early phase and delayed phase was lower in the radiation group than in the control group (P < 0.05). The AT rate in the lateral olfactory tracts (LOT) and the transsynaptic AT rate were significantly lower in the irradiated rats than in the control rats (P < 0.05). The levels of the motor proteins kinesin-1 and cytoplasmic dynein were significantly decreased in the irradiation group (P < 0.05). The expression of the energy metabolism-related proteins ATPB and COX IV was significantly lower in the irradiated rats than in the control rats (P < 0.05). Apoptosis and synaptic damage were observed after irradiation.
MRI of the olfactory pathway can be used to assess AT impairment in RIBI models. AT deficits secondary to radiation damage are the result of multiple factors, including declines in motor protein levels, neuronal apoptosis, synaptic damage and energy metabolism dysfunction. Cranial irradiation-induced sexual dysfunction was associated with decreased sex hormone levels secondary to hypothalamic-pituitary-gonadal axis injury.
本研究旨在评估放射性脑损伤（RIBI）对轴突运输（AT）和性功能的影响。
成年雄性大鼠接受全脑照射，总剂量为 30Gy（15Gy 分 2 次），以建立 RIBI 模型。在脑照射 8 周后评估觅食行为和性功能，并进行 MRI 检查。在将 MnCl2 灌注到大鼠鼻腔后，进行 MRI 的早期和延迟相检查。通过 Western 印迹法测定运动蛋白水平以及与能量代谢和 AT 相关的蛋白水平。通过 ELISA 测定血液中性激素水平。用透射电子显微镜进行超微结构分析。
脑照射后大鼠的觅食能力下降，照射组的觅食时间长于对照组（P<0.05）。照射组大鼠的性功能明显下降。与对照组大鼠相比，照射组大鼠的血清睾酮、FSH、LH 和 GnRH 水平显著降低（P<0.001）。早期和延迟相时，照射组嗅球（OB）中 Mn 的摄取量低于对照组（P<0.05）。照射组外侧嗅束（LOT）和突触间 AT 率明显低于对照组（P<0.05）。照射组的运动蛋白 kinesin-1 和细胞质动力蛋白的水平明显降低（P<0.05）。照射组的能量代谢相关蛋白 ATPB 和 COX IV 的表达明显低于对照组（P<0.05）。照射后观察到细胞凋亡和突触损伤。
嗅觉通路的 MRI 可用于评估 RIBI 模型中的 AT 损伤。放射损伤导致的 AT 缺陷是多种因素的结果，包括运动蛋白水平下降、神经元凋亡、突触损伤和能量代谢功能障碍。颅照射引起的性功能障碍与下丘脑-垂体-性腺轴损伤导致的性激素水平下降有关。
