谷氨酸调节剂利鲁唑可逆转年龄和阿尔茨海默病的基因表达谱。
Age and Alzheimer's disease gene expression profiles reversed by the glutamate modulator riluzole.
作者信息
Pereira A C, Gray J D, Kogan J F, Davidson R L, Rubin T G, Okamoto M, Morrison J H, McEwen B S
机构信息
Laboratory of Neuroendocrinology, Department of Neuroscience, The Rockefeller University, New York, NY, USA.
Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sports Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
出版信息
Mol Psychiatry. 2017 Feb;22(2):296-305. doi: 10.1038/mp.2016.33. Epub 2016 Mar 29.
Alzheimer's disease (AD) and age-related cognitive decline represent a growing health burden and involve the hippocampus, a vulnerable brain region implicated in learning and memory. To understand the molecular effects of aging on the hippocampus, this study characterized the gene expression changes associated with aging in rodents using RNA-sequencing (RNA-seq). The glutamate modulator, riluzole, which was recently shown to improve memory performance in aged rats, prevented many of the hippocampal age-related gene expression changes. A comparison of the effects of riluzole in rats against human AD data sets revealed that many of the gene changes in AD are reversed by riluzole. Expression changes identified by RNA-Seq were validated by qRT-PCR open arrays. Riluzole is known to increase the glutamate transporter EAAT2's ability to scavenge excess glutamate, regulating synaptic transmission. RNA-seq and immunohistochemistry confirmed an increase in EAAT2 expression in hippocampus, identifying a possible mechanism underlying the improved memory function after riluzole treatment.
阿尔茨海默病（AD）和与年龄相关的认知衰退给健康带来了日益沉重的负担，且涉及海马体，这是一个与学习和记忆相关的脆弱脑区。为了解衰老对海马体的分子影响，本研究利用RNA测序（RNA-seq）对啮齿动物衰老过程中相关的基因表达变化进行了表征。谷氨酸调节剂利鲁唑最近被证明可改善老年大鼠的记忆表现，它能预防许多与海马体衰老相关的基因表达变化。将利鲁唑对大鼠的影响与人类AD数据集进行比较后发现，AD中的许多基因变化可被利鲁唑逆转。通过qRT-PCR开放阵列验证了RNA-Seq鉴定出的表达变化。已知利鲁唑可增强谷氨酸转运体EAAT2清除过量谷氨酸的能力，从而调节突触传递。RNA测序和免疫组织化学证实海马体中EAAT2表达增加，这确定了利鲁唑治疗后记忆功能改善的潜在机制。
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