A chlorzoxazone-folic acid combination improves cognitive affective decline in SCA2-58Q mice.
A chlorzoxazone-folic acid combination improves cognitive affective decline in SCA2-58Q mice.
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DOI：
10.1038/s41598-023-39331-y
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发表时间：
2023-08-03
影响因子：
4.6
通讯作者：
Egorova, Polina A.
中科院分区：
文献类型：
--
作者：
Marinina, Ksenia S.;Bezprozvanny, Ilya B.;Egorova, Polina A.
脊髓小脑性共济失调 2 型 (SCA2) 是一种多聚谷氨酰胺疾病，由 ATXN2 基因中 CAG 重复序列的病理性扩增引起。 SCA2 伴有小脑变性和进行性运动能力下降。小脑浦肯野细胞 (PC) 似乎主要受到这种疾病的影响。大多数共济失调研究都集中在共济失调患者和该疾病的动物模型中观察到的运动衰退。然而，最近来自患者和共济失调小鼠的证据表明，SCA2 也可能具有小脑认知情感综合征的症状。我们之前报道过 SCA2-58Q PC 特异性转基因小鼠表现出抗焦虑行为、空间记忆下降和抑郁样状态。在这里，我们研究了氯唑沙宗 (CHZ) 联合叶酸 (FA) 激活小电导钙激活钾通道（SK 通道）对 SCA2-58Q 小鼠 PC 放电以及运动、认知和情感症状的影响。我们意识到 CHZ-FA 组合改善了 SCA2-58Q 小鼠的运动和认知衰退以及情绪改变，而不影响其小脑 PC 的放电率。我们的结果支持了对共济失调小鼠的共济失调和非运动症状进行联合治疗而不影响 PC 放电频率的想法。
Spinocerebellar ataxia type 2 (SCA2) is a polyglutamine disorder caused by a pathological expansion of CAG repeats in ATXN2 gene. SCA2 is accompanied by cerebellar degeneration and progressive motor decline. Cerebellar Purkinje cells (PCs) seem to be primarily affected in this disorder. The majority of the ataxia research is focused on the motor decline observed in ataxic patients and animal models of the disease. However, recent evidence from patients and ataxic mice suggests that SCA2 can also share the symptoms of the cerebellar cognitive affective syndrome. We previously reported that SCA2-58Q PC-specific transgenic mice exhibit anxiolytic behavior, decline in spatial memory, and a depressive-like state. Here we studied the effect of the activation of the small conductance calcium-activated potassium channels (SK channels) by chlorzoxazone (CHZ) combined with the folic acid (FA) on the PC firing and also motor, cognitive and affective symptoms in SCA2-58Q mice. We realized that CHZ-FA combination improved motor and cognitive decline as well as ameliorated mood alterations in SCA2-58Q mice without affecting the firing rate of their cerebellar PCs. Our results support the idea of the combination therapy for both ataxia and non-motor symptoms in ataxic mice without affecting the firing frequency of PCs.
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影响因子：
3.3
作者：
Eckart, S.;Hoertnag, H.;Hellweg, R.
通讯作者：
Hellweg, R.
影响因子：
5.6
作者：
Bai, Yanyan;Ma, Xinshun
通讯作者：
Ma, Xinshun
DOI：
10.1016/j.bbamcr.2023.119466
发表时间：
2023-03-21
影响因子：
5.1
作者：
Egorova, Polina A.;Marinina, Ksenia S.;Bezprozvanny, Ilya B.
通讯作者：
Bezprozvanny, Ilya B.
影响因子：
7.3
作者：
El-Sayed NS;Nam YW;Egorova PA;Nguyen HM;Orfali R;Rahman MA;Yang G;Wulff H;Bezprozvanny I;Parang K;Zhang M
通讯作者：
Zhang M
在清醒的转基因小鼠中对小脑Purkinje细胞自发性射击的体内分析，该小鼠模拟了2型脊椎动物共济失调。
影响因子：
4
作者：
Egorova PA;Gavrilova AV;Bezprozvanny IB
通讯作者：
Bezprozvanny IB