SIRT6过表达影响海马CA1长期恐惧记忆形成:一项新发现

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本文研究的焦点是"Overexpression of SIRT6 in the hippocampal CA1 impairs the formation of long-term contextual fear memory",发表在《中国科技论文在线》上。作者尹希、宋利等人,分别来自河北医科大学第四医院、生物化学与分子生物学系、河北省老年心血管病医院以及华北军区白求恩和平医院,他们的研究得到了中国自然科学基金(81201038, 31371140)、河北省优秀青年基金等多个机构的支持。 SIRT6是一种沉默信息调节蛋白,它在细胞内通过调控组蛋白修饰发挥关键作用。海马CA1脑区是大脑中与学习和记忆形成密切相关的结构,特别是与长期环境关联的记忆,如恐惧记忆。研究发现,通过环境关联的恐惧训练,会显著下调海马CA1区域的SIRT6水平。这一现象表明SIRT6可能在恐惧记忆的建立过程中扮演了抑制性角色。 实验部分可能涉及将SIRT6过度表达于大鼠的海马CA1脑区,观察其对恐惧记忆形成的影响。结果可能是,高表达的SIRT6抑制了神经元之间的信号传递,影响了长期记忆形成过程中的特定通路,如与乙酰化调控相关的信号传导。这可能涉及到DNA和组蛋白的稳定,从而影响基因表达和神经元功能。 值得注意的是,这项研究的作者尹希博士是一位神经内分泌学专家,她的工作可能侧重于理解神经递质如何与SIRT6相互作用,以及这种交互如何影响记忆形成和调节。论文的通讯作者石海石博士则是该领域的青年才俊,他的研究兴趣可能集中在寻找新的治疗策略,以通过调控SIRT6来改善记忆障碍,例如在恐惧症等神经精神疾病中的应用。 这篇首发论文揭示了SIRT6在海马CA1中对长期环境关联恐惧记忆形成的重要性,并为进一步探索SIRT6在神经生物学和神经心理学领域提供了新的视角和潜在干预靶点。这些发现对于理解记忆机制,尤其是恐惧记忆的存储和巩固,具有重要的理论和临床价值。

Rab GTPases serve as master regulators of membrane trafficking. They can be activated by guanine nucleotide exchange factors (GEF) and be inactivated by GTPase-activating proteins (GAPs). The roles of some GAPs have been explored in Saccharomyces cerevisiae, but are largely unknown in filamentous fungi. Here, we investigated the role of GAP Gyp3 gene, an ortholog of S. cerevisiae Gyp3, in an entomopathogenic fungus, Metarhizium acridum. We found that MaGyp3 is mainly localized to the endoplasmic reticulum (ER) of vegetative hyphae, nuclei of mature conidia, and both ER and nuclei in invasive hyphae. Lack of MaGyp3 caused a decreased tolerance to hyperosmotic stress, heat-shock and UV-B radiation. Moreover, the ΔMaGyp3 mutant showed a significantly decreased pathogenicity owing to delayed germination, reduced appressorium-mediated penetration and impaired invasive growth. Loss of MaGyp3 also caused impaired fungal growth, advanced conidiation and defects in utilization of carbon and nitrogen sources, while overexpression of MaGyp3 exhibited delayed conidiation on nutrient-rich medium and conidiation pattern shift from microcycle conidiation to normal conidiation on nutrient-limited medium. Mavib-1, a tanscription factor invloved in conidiation by affecting nutrient utilizaiton, can directly bind to the promoter of MaGyp3. ΔMaGyp3 and ΔMavib-1 mutants shared similar phenotypes, and overexpression mutants of MaGyp3 and Mavib-1 (Mavib-1-OE) exhibited similar phenotypes in growth, conidiation and pathogenicity. Reintroduction of the Magyp3 driven by strong promoter gpd in ΔMavib-1 mutant recovered the defects in growth and conidiation for dysfunction of Mavib1. Taken together, our findings uncovered the role of GAP3 in a filamentous pathogenic fungus and and illustrated the upstream regulatory mechanism by direct interaction with Mavib-1.

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