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视黄酸对成年海马颗粒细胞活性和空间辨别能力的调节作用。

Retinoic acid modulation of granule cell activity and spatial discrimination in the adult hippocampus.

作者信息

Yeo Yun-Gwon, Park Jeongrak, Kim Yoonsub, Rah Jong-Cheol, Shin Chang-Hoon, Oh Seo-Jin, Jang Jin-Hyeok, Lee Yaebin, Yoon Jong Hyuk, Oh Yong-Seok

机构信息

Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea.

Sensory and Motor Systems Research Group, Korea Brain Research Institute (KBRI), Daegu, Republic of Korea.

出版信息

Front Cell Neurosci. 2024 Apr 17;18:1379438. doi: 10.3389/fncel.2024.1379438. eCollection 2024.

Abstract

Retinoic acid (RA), derived from vitamin A (retinol), plays a crucial role in modulating neuroplasticity within the adult brain. Perturbations in RA signaling have been associated with memory impairments, underscoring the necessity to elucidate RA's influence on neuronal activity, particularly within the hippocampus. In this study, we investigated the cell type and sub-regional distribution of RA-responsive granule cells (GCs) in the mouse hippocampus and delineated their properties. We discovered that RA-responsive GCs tend to exhibit a muted response to environmental novelty, typically remaining inactive. Interestingly, chronic dietary depletion of RA leads to an abnormal increase in GC activation evoked by a novel environment, an effect that is replicated by the localized application of an RA receptor beta (RARβ) antagonist. Furthermore, our study shows that prolonged RA deficiency impairs spatial discrimination-a cognitive function reliant on the hippocampus-with such impairments being reversible with RA replenishment. In summary, our findings significantly contribute to a better understanding of RA's role in regulating adult hippocampal neuroplasticity and cognitive functions.

摘要

视黄酸(RA)由维生素A(视黄醇)衍生而来,在调节成人大脑的神经可塑性方面发挥着关键作用。RA信号通路的紊乱与记忆障碍有关,这凸显了阐明RA对神经元活动影响的必要性,尤其是在海马体内。在本研究中,我们调查了小鼠海马体中对RA有反应的颗粒细胞(GCs)的细胞类型和亚区域分布,并描述了它们的特性。我们发现,对RA有反应的GCs往往对环境新奇性表现出微弱反应,通常保持不活跃状态。有趣的是,长期通过饮食消耗RA会导致新环境诱发的GC激活异常增加,局部应用RA受体β(RARβ)拮抗剂也会产生同样的效果。此外,我们的研究表明,长期缺乏RA会损害空间辨别能力——一种依赖海马体的认知功能——而补充RA后这种损害是可逆的。总之,我们的研究结果为更好地理解RA在调节成人海马体神经可塑性和认知功能中的作用做出了重要贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91a3/11061364/ee2f041b210f/fncel-18-1379438-g001.jpg

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