Sex Differences in the Behavioural Aspects of the Cuprizone-Induced Demyelination Model in Mice.
Sex Differences in the Behavioural Aspects of the Cuprizone-Induced Demyelination Model in Mice.
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DOI：
10.3390/brainsci12121687
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发表时间：
2022-12-08
期刊：
影响因子：
3.3
通讯作者：
Kivell, Bronwyn M.
中科院分区：
文献类型：
--
作者：
Paton, Kelly F.;Hong, Sheein;Biggerstaff, Andrew;Kivell, Bronwyn M.
多发性硬化症是一种自身免疫性疾病，其特征是中枢神经系统的脱髓鞘。铜腙诱导的脱髓鞘模型经常用于小鼠中，以测试多发性硬化症的新疗法。然而，尽管有显著的脱髓鞘，行为缺陷可能是微妙的或具有混合的结果，这取决于所使用的范例。此外，模型中的性别差异还没有得到很好的理解。在目前的研究中，我们试图了解行为缺陷与cuprizone诱导的脱髓鞘模型在雄性和雌性C57 BL/6 J小鼠。使用黑金II染色，我们发现，cuprizone给药超过6周导致胼胝体显著脱髓鞘，这在两种性别之间是一致的。当使用电子von Frey触觉计测量时，Cuprizone给药引起机械敏感性增加，未观察到性别差异。然而，cuprizone管理减少运动协调，与更严重的赤字中看到的男性在单杠和被动线挂测试。相比之下，雌性小鼠在运动技能序列测试中表现出更严重的缺陷。在高架零迷宫中，与雌性动物相比，铜腙给药引起雄性动物更多的焦虑样行为。因此，这项研究提供了一个更好的理解，在行为方面的铜腙诱导脱髓鞘，这可以让一个更好的翻译结果从实验室到临床参与的性别差异。
Multiple sclerosis is an autoimmune disease characterised by demyelination in the central nervous system. The cuprizone-induced demyelination model is often used in mice to test novel treatments for multiple sclerosis. However, despite significant demyelination, behavioural deficits may be subtle or have mixed results depending on the paradigm used. Furthermore, the sex differences within the model are not well understood. In the current study, we have sought to understand the behavioural deficits associated with the cuprizone-induced demyelination model in both male and female C57BL/6J mice. Using Black gold II stain, we found that cuprizone administration over 6 weeks caused significant demyelination in the corpus callosum that was consistent across both sexes. Cuprizone administration caused increased mechanical sensitivity when measured using an electronic von Frey aesthesiometer, with no sex differences observed. However, cuprizone administration decreased motor coordination, with more severe deficits seen in males in the horizontal bar and passive wire hang tests. In contrast, female mice showed more severe deficits in the motor skill sequence test. Cuprizone administration caused more anxiety-like behaviours in males compared to females in the elevated zero maze. Therefore, this study provides a better understanding of the sex differences involved in the behavioural aspects of cuprizone-induced demyelination, which could allow for a better translation of results from the laboratory to the clinic.
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