Sexual dimorphism in neurological function after SCI is associated with disrupted neuroinflammation in both injured spinal cord and brain.
Sexual dimorphism in neurological function after SCI is associated with disrupted neuroinflammation in both injured spinal cord and brain.
复制标题
DOI：
10.1016/j.bbi.2021.12.017
复制
发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Li Y;Ritzel RM;Lei Z;Cao T;He J;Faden AI;Wu J
虽然人类脊髓损伤（SCI）在男性中更为常见，但女性中的患病率正在增加。然而，人们对生物性别对大脑功能障碍和损伤机制的影响知之甚少。为了模拟人类最高的人均受伤率（年龄在 16-30 岁之间），在本研究中，对年轻成年或年轻/中年雄性和雌性 C57BL/6 小鼠进行中度挫伤 SCI。当小鼠在 10-12 周大时受伤时，对炎症相关基因的转录组分析和流式细胞术显示，在 3 d SCI 后，雄性小鼠的神经炎症特征比雌性更强，表面上是由性别特异性改变骨髓细胞功能而不是细胞数量驱动的。雌性小鼠在基线时通常更活跃，这可以从在开阔场地中移动更远的距离来证明。 SCI后，雌性小鼠比雄性小鼠具有更好的运动功能。受伤后 13 周，雄性小鼠在认知和抑郁样行为测试中表现不佳，而受伤的雌性小鼠在这些任务中表现出较少的缺陷。然而，当在 6 个月大时受伤，随后在受伤后 8 个月时，雄性小鼠与雌性小鼠相比，尽管在情感、认知和运动任务方面具有相似或更差的结果，但炎症激活要少得多。总的来说，这些发现表明 SCI 后功能结果的性别差异与损伤发生时的年龄以及损伤部位和远端大脑区域的神经炎症破坏有关。因此，在设计新的治疗药物时应考虑生物性别。
Whereas human spinal cord injury (SCI) is more common in men, the prevalence is growing in women. However, little is known about the effect of biological sex on brain dysfunction and injury mechanisms. To model the highest per capita rate of injury (ages between 16–30 years old) in humans, in the present study, young adult or a young/middle-aged male and female C57BL/6 mice were subjected to moderate contusion SCI. When mice were injured at 10–12-week-old, transcriptomic analysis of inflammation-related genes and flow cytometry revealed a more aggressive neuroinflammatory profile in male than females following 3 d SCI, ostensibly driven by sex-specific changes myeloid cell function rather than cell number. Female mice were generally more active at baseline, as evidenced by greater distance traveled in the open field. After SCI, female mice had more favorable locomotor function than male animals. At 13 weeks post-injury, male mice showed poor performance in cognitive and depressive-like behavioral tests, while injured female mice showed fewer deficits in these tasks. However, when injured at 6 months old followed by 8 months post-injury, male mice had considerably less inflammatory activation compared with female animals despite having similar or worse outcomes in affective, cognitive, and motor tasks. Collectively, these findings indicate that sex differences in functional outcome after SCI are associated with the age at onset of injury, as well as disrupted neuroinflammation not only at the site of injury but also in remote brain regions. Thus, biological sex should be considered when designing new therapeutic agents.
登录
查看更多内容
影响因子：
3.4
作者：
Hauben, E;Mizrahi, T;Schwartz, M
通讯作者：
Schwartz, M
影响因子：
4.2
作者：
Datto, Jeffrey P.;Bastidas, Johana C.;Pearse, Damien D.
通讯作者：
Pearse, Damien D.
影响因子：
7.9
作者：
Comfort N;Re DB
通讯作者：
Re DB
影响因子：
2.5
作者：
Byers, James S.;Huguenard, Anna L.;Kuruppu, Dulanji;Liu, Nai-Kui;Xu, Xiao-Ming;Sengelaub, Dale R.
通讯作者：
Sengelaub, Dale R.
影响因子：
4.2
作者：
Fukutoku, Tatsuhiro;Kumagai, Gentaro;Ishibashi, Yasuyuki
通讯作者：
Ishibashi, Yasuyuki