Newfound sex differences in axonal structure underlie differential outcomes from in vitro traumatic axonal injury.

Newfound sex differences in axonal structure underlie differential outcomes from in vitro traumatic axonal injury.
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轴突结构的新发现的性别差异是体外创伤性轴突损伤的差异结果。

DOI:
10.1016/j.expneurol.2017.11.001
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发表时间:
2018-03
影响因子:
5.3
通讯作者:
Smith DH
Smith DH
中科院分区:
医学2区
文献类型:
--
作者:
Dollé JP;Jaye A;Anderson SA;Ahmadzadeh H;Shenoy VB;Smith DH

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由于创伤性轴突损伤 (TAI) 被认为是脑震荡的一种重要病理学,我们研究了轴突结构和对 TAI 反应的潜在性别差异。大鼠和人类神经元被用来在体外发育微图案轴突束,这些轴突束在遗传上是雄性或雌性。超微结构分析首次揭示,女性轴突比男性轴突更小,微管更少。 TAI 的计算模型表明,这些结构差异使女性轴突中的微管在相同的外加载荷下,在创伤期间比男性轴突中的微管失效的风险更大。同样,在 TAI 的体外模型中,轴突束的动态拉伸损伤比男性轴突诱导了更多的女性轴突病理生理学,包括微管机械断裂导致更广泛的波动形成,以及相同水平损伤后不久的更多钙流入。损伤后 24 小时,女性轴突比男性轴突表现出明显更多的肿胀和更大的钙信号功能丧失。因此,与遭受相同机械损伤的男性相比,大脑中轴突结构的性别二态性也可能导致女性更广泛的轴突病理学。
Since traumatic axonal injury (TAI) is implicated as a prominent pathology of concussion, we examined potential sex differences in axon structure and responses to TAI. Rat and human neurons were used to develop micro-patterned axon tracts in vitro that were genetically either male or female. Ultrastructural analysis revealed for the first time that female axons were consistently smaller with fewer microtubules than male axons. Computational modeling of TAI showed that these structural differences place microtubules in female axons at greater risk of failure during trauma under the same applied loads than in male axons. Likewise, in an in vitro model of TAI, dynamic stretch-injury to axon tracts induced greater pathophysiology of female axons than male axons, including more extensive undulation formations resulting from mechanical breaking of microtubules, and greater calcium influx shortly after the same level of injury. At 24 h post-injury, female axons exhibited significantly more swellings and greater loss of calcium signaling function than male axons. Accordingly, sexual dimorphism of axon structure in the brain may also contribute to more extensive axonal pathology in females compared to males exposed to the same mechanical injury.
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发表时间: 1994-08
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