In-vivo genetic ablation of metabotropic glutamate receptor type 5 slows down disease progression in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis.

来自 PUBMED

作者:

Bonifacino TProvenzano FGallia ERavera STorazza CBossi SFerrando SPuliti AVan Den Bosch LBonanno GMilanese M

展开

摘要:

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease due to motor neuron (MN) loss. The mechanisms causing selective MN death are largely unknown, thus prejudicing successful pharmacological treatments. Major causes of MN damage are effects downstream of the abnormal glutamate (Glu) neurotransmission. Group I metabotropic Glu receptors (mGluR1, mGluR5) actively contribute to the excitotoxicity in ALS and represent druggable molecular targets. We previously demonstrated that halving mGluR1 or mGluR5 expression in the widely studied SOD1G93A mouse model of ALS had a positive impact on disease onset, clinical progression and survival, as well as on cellular and biochemical parameters altered in ALS. Whereas these effects were similar in female and male mGluR1 heterozygous SOD1G93Amice, only male mGluR5 heterozygous SOD1G93A mice showed improved motor skills during disease progression. To further validate the role of Group I mGluRs in ALS, we generated in this study mGluR1 or mGluR5 null mice expressing the SOD1G93A mutation (SOD1G93AGrm1crv4/crv4 or SOD1G93AGrm5-/-, respectively). SOD1G93AGrm1crv4/crv4 mice showed early and progressive motor impairments and died even before SOD1G93A mice, while SOD1G93AGrm5-/- mice exhibited delayed disease onset, longer survival, and ameliorated motor skills than SOD1G93A mice. No difference between female and male SOD1G93AGrm5-/- mice were observed. These effects were associated with enhanced MN preservation and decreased astrocytic and microglial activation. Our results strongly support the assumption that constitutively lowering of mGluR5 expression has a positive impact in mice with ALS by counteracting the abnormal Glu transmission and this could be a potentially effective pharmacological target in ALS.

收起

展开

DOI:

10.1016/j.nbd.2019.05.007

被引量:

11

年份:

1970

SCI-Hub (全网免费下载) 发表链接

通过 文献互助 平台发起求助,成功后即可免费获取论文全文。

查看求助

求助方法1:

知识发现用户

每天可免费求助50篇

求助

求助方法1:

关注微信公众号

每天可免费求助2篇

求助方法2:

求助需要支付5个财富值

您现在财富值不足

您可以通过 应助全文 获取财富值

求助方法2:

完成求助需要支付5财富值

您目前有 1000 财富值

求助

我们已与文献出版商建立了直接购买合作。

你可以通过身份认证进行实名认证,认证成功后本次下载的费用将由您所在的图书馆支付

您可以直接购买此文献,1~5分钟即可下载全文,部分资源由于网络原因可能需要更长时间,请您耐心等待哦~

身份认证 全文购买

相似文献(1154)

参考文献(0)

引证文献(11)

来源期刊

-

影响因子:暂无数据

JCR分区: 暂无

中科院分区:暂无

研究点推荐

关于我们

zlive学术集成海量学术资源,融合人工智能、深度学习、大数据分析等技术,为科研工作者提供全面快捷的学术服务。在这里我们不忘初心,砥砺前行。

友情链接

联系我们

合作与服务

©2024 zlive学术声明使用前必读