Hippocampal TMEM55B overexpression in the 5XFAD mouse model of Alzheimer's disease

IF 2.4 3区 医学 Q3 NEUROSCIENCES Hippocampus Pub Date : 2023-11-14 DOI:10.1002/hipo.23586
Kristian F. Odfalk, Jessica L. Wickline, Sabrina Smith, Radek Dobrowolski, Sarah C. Hopp
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Abstract

Dysfunction of the endosomal-lysosomal network is a notable feature of Alzheimer's disease (AD) pathology. Dysfunctional endo-lysosomal vacuoles accumulate in dystrophic neurites surrounding amyloid β (Aβ) plaques and may be involved in the pathogenesis and progression of Aβ aggregates. Trafficking and thus maturation of these dysfunctional vacuoles is disrupted in the vicinity of Aβ plaques. Transmembrane protein 55B (TMEM55B), also known as phosphatidylinositol-4,5-bisphosphate 4-phosphatase 1 (PIP4P1) is an endo-lysosomal membrane protein that is necessary for appropriate trafficking of endo-lysosomes. The present study tested whether overexpression of TMEM55B in the hippocampus could prevent plaque-associated axonal accumulation of dysfunctional endo-lysosomes, reduce Aβ plaque load, and prevent hippocampal-dependent learning and memory deficits in the 5XFAD mouse models of Aβ plaque pathology. Immunohistochemical analyses revealed a modest but significant reduction in the accumulation of endo-lysosomes in dystrophic neurites surrounding Aβ plaques, but there was no change in hippocampal-dependent memory or plaque load. Overall, these data indicate a potential role for TMEM55B in reducing endo-lysosomal dysfunction during AD-like Aβ pathology.

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阿尔茨海默病小鼠5XFAD模型海马TMEM55B过表达
内体-溶酶体网络功能障碍是阿尔茨海默病(AD)病理的一个显著特征。功能失调的内溶酶体空泡积聚在β淀粉样蛋白(Aβ)斑块周围的营养不良神经突中,可能参与了β淀粉样蛋白聚集的发病和进展。在Aβ斑块附近,这些功能失调的空泡的运输和成熟被破坏。跨膜蛋白55B (TMEM55B),也称为磷脂酰肌醇-4,5-二磷酸4-磷酸酶1 (PIP4P1)是内溶酶体膜蛋白,是内溶酶体适当运输所必需的。本研究在Aβ斑块病理的5XFAD小鼠模型中测试了海马中TMEM55B的过表达是否可以阻止斑块相关的功能失调内溶酶体轴突积聚,减少Aβ斑块负荷,并预防海马依赖性学习和记忆缺陷。免疫组织化学分析显示,在a β斑块周围的营养不良神经突中,内溶酶体的积累适度但显著减少,但海马依赖性记忆或斑块负荷没有改变。总的来说,这些数据表明TMEM55B在ad样a β病理过程中减少内溶酶体功能障碍的潜在作用。
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来源期刊
Hippocampus
Hippocampus 医学-神经科学
CiteScore
5.80
自引率
5.70%
发文量
79
审稿时长
3-8 weeks
期刊介绍: Hippocampus provides a forum for the exchange of current information between investigators interested in the neurobiology of the hippocampal formation and related structures. While the relationships of submitted papers to the hippocampal formation will be evaluated liberally, the substance of appropriate papers should deal with the hippocampal formation per se or with the interaction between the hippocampal formation and other brain regions. The scope of Hippocampus is wide: single and multidisciplinary experimental studies from all fields of basic science, theoretical papers, papers dealing with hippocampal preparations as models for understanding the central nervous system, and clinical studies will be considered for publication. The Editor especially encourages the submission of papers that contribute to a functional understanding of the hippocampal formation.
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