文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

氯唑沙宗-叶酸联合改善 SCA2-58Q 小鼠的认知情感下降。

A chlorzoxazone-folic acid combination improves cognitive affective decline in SCA2-58Q mice.

机构信息

Laboratory of Molecular Neurodegeneration, Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia.

Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

出版信息

Sci Rep. 2023 Aug 3;13(1):12588. doi: 10.1038/s41598-023-39331-y.


DOI:10.1038/s41598-023-39331-y
PMID:37537226
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10400576/
Abstract

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.

摘要

脊髓小脑共济失调 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张引起。SCA2 伴有小脑变性和进行性运动下降。小脑浦肯野细胞(PCs)似乎是该疾病的主要受影响细胞。大多数共济失调研究都集中在共济失调患者和疾病动物模型中观察到的运动下降上。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焦虑样行为、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 联合治疗改善了 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 PCs 的放电率。我们的结果支持在不影响 PCs 放电频率的情况下,对共济失调小鼠进行联合治疗以治疗共济失调和非运动症状的想法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe6f/10400576/5235bcac3d5d/41598_2023_39331_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe6f/10400576/ba1a8f8d70c0/41598_2023_39331_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe6f/10400576/45eb35dc1251/41598_2023_39331_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe6f/10400576/e9cc4d12d24f/41598_2023_39331_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe6f/10400576/2a3b4ec372de/41598_2023_39331_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe6f/10400576/8289b37009a0/41598_2023_39331_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe6f/10400576/8927fccae692/41598_2023_39331_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe6f/10400576/5235bcac3d5d/41598_2023_39331_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe6f/10400576/ba1a8f8d70c0/41598_2023_39331_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe6f/10400576/45eb35dc1251/41598_2023_39331_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe6f/10400576/e9cc4d12d24f/41598_2023_39331_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe6f/10400576/2a3b4ec372de/41598_2023_39331_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe6f/10400576/8289b37009a0/41598_2023_39331_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe6f/10400576/8927fccae692/41598_2023_39331_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe6f/10400576/5235bcac3d5d/41598_2023_39331_Fig7_HTML.jpg

相似文献

[1]
A chlorzoxazone-folic acid combination improves cognitive affective decline in SCA2-58Q mice.

Sci Rep. 2023-8-3

[2]
In vivo analysis of the spontaneous firing of cerebellar Purkinje cells in awake transgenic mice that model spinocerebellar ataxia type 2.

Cell Calcium. 2021-1

[3]
Electrophysiological Studies Support Utility of Positive Modulators of SK Channels for the Treatment of Spinocerebellar Ataxia Type 2.

Cerebellum. 2022-10

[4]
In vivo analysis of cerebellar Purkinje cell activity in SCA2 transgenic mouse model.

J Neurophysiol. 2016-6-1

[5]
Cognitive Decline and Mood Alterations in the Mouse Model of Spinocerebellar Ataxia Type 2.

Cerebellum. 2024-2

[6]
A combination of chlorzoxazone and folic acid improves recognition memory, anxiety and depression in SCA3-84Q mice.

Hum Mol Genet. 2024-8-6

[7]
Deranged calcium signaling and neurodegeneration in spinocerebellar ataxia type 2.

J Neurosci. 2009-7-22

[8]
Chronic suppression of STIM1-mediated calcium signaling in Purkinje cells rescues the cerebellar pathology in spinocerebellar ataxia type 2.

Biochim Biophys Acta Mol Cell Res. 2023-6

[9]
In Vivo Analysis of the Climbing Fiber-Purkinje Cell Circuit in SCA2-58Q Transgenic Mouse Model.

Cerebellum. 2018-10

[10]
Ataxic Symptoms in Huntington's Disease Transgenic Mouse Model Are Alleviated by Chlorzoxazone.

Front Neurosci. 2020-4-3

引用本文的文献

[1]
Therapeutic efficacy of the BKCa channel opener chlorzoxazone in a mouse model of Fragile X syndrome.

Neuropsychopharmacology. 2024-12

[2]
A combination of chlorzoxazone and folic acid improves recognition memory, anxiety and depression in SCA3-84Q mice.

Hum Mol Genet. 2024-8-6

[3]
Memory decline, anxiety and depression in the mouse model of spinocerebellar ataxia type 3.

Hum Mol Genet. 2024-2-1

本文引用的文献

[1]
Chronic suppression of STIM1-mediated calcium signaling in Purkinje cells rescues the cerebellar pathology in spinocerebellar ataxia type 2.

Biochim Biophys Acta Mol Cell Res. 2023-6

[2]
Cognitive Decline and Mood Alterations in the Mouse Model of Spinocerebellar Ataxia Type 2.

Cerebellum. 2024-2

[3]
Electrophysiological Studies Support Utility of Positive Modulators of SK Channels for the Treatment of Spinocerebellar Ataxia Type 2.

Cerebellum. 2022-10

[4]
Structure-Activity Relationship Study of Subtype-Selective Positive Modulators of K2 Channels.

J Med Chem. 2022-1-13

[5]
Behavioral and neurochemical effects of folic acid in a mouse model of depression induced by TNF-α.

Behav Brain Res. 2021-9-24

[6]
Cognitive deficits in episodic ataxia type 2 mouse models.

Hum Mol Genet. 2021-9-15

[7]
Gray matter networks associated with attention and working memory deficit in ADHD across adolescence and adulthood.

Transl Psychiatry. 2021-3-25

[8]
Cognitive impairment and its neuroimaging correlates in spinocerebellar ataxia 2.

Parkinsonism Relat Disord. 2021-4

[9]
Evaluation of the Behavioural, Antioxidative and Histomorphological Effects of Folic Acid-supplemented Diet in Dexamethasone-induced Depression in Mice.

Cent Nerv Syst Agents Med Chem. 2021

[10]
Mood alterations in mouse models of Spinocerebellar Ataxia type 1.

Sci Rep. 2021-1-12

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索