4.7 Article

High levels of 27-hydroxycholesterol results in synaptic plasticity alterations in the hippocampus

期刊

SCIENTIFIC REPORTS
卷 11, 期 1, 页码 -

出版社

NATURE PORTFOLIO
DOI: 10.1038/s41598-021-83008-3

关键词

-

资金

  1. Margaretha af Ugglas Stiftelse
  2. Gun och Bertil Stohnes Stiftelse
  3. Karolinska Institutet fund for geriatric research
  4. Stiftelsen Gamla Tjanarinnor
  5. Tore Nilsson Stiftelse
  6. EMBO Long-Term Fellowship [ALFT 696-2013]
  7. SSMF postdoctoral Fellowship
  8. Juan de la Cierva [IJCI-2016-27658]
  9. CONACYT (Mexico) [CVU: 209252, 232099]
  10. Lindhes Advokatbyra Foundation
  11. Stockholm County Council
  12. Karolinska Institutet
  13. Centro de Investigacion en Red sobre Enfermedades Neurodegenerativas (CIBERNED) [CB06/05/0066]
  14. Ministerio de Ciencia, Innovacion y Universidades [PGC2018-094307-B-I00]
  15. Knut and Alice Wallenberg Foundation
  16. Swedish Research Council
  17. Centre for Innovative Medicine
  18. Jonasson Center at the Royal Institute of Technology, Sweden
  19. Demensfonden

向作者/读者索取更多资源

Elevated levels of 27-hydroxycholesterol (27-OH) enhance long-term potentiation (LTP) in Schaffer collateral-CA1 synapses and lead to abnormally large dendritic spines in the stratum radiatum. Cyp27Tg mice show a significantly higher density of synaptopodin-positive puncta in CA1. High 27-OH levels may alter synaptic potentiation and disrupt fine-tuned processing of information in hippocampal circuits, potentially causing cognitive impairment.
Alterations in brain cholesterol homeostasis in midlife are correlated with a higher risk of developing Alzheimer's disease (AD). However, global cholesterol-lowering therapies have yielded mixed results when it comes to slowing down or preventing cognitive decline in AD. We used the transgenic mouse model Cyp27Tg, with systemically high levels of 27-hydroxycholesterol (27-OH) to examine long-term potentiation (LTP) in the hippocampal CA1 region, combined with dendritic spine reconstruction of CA1 pyramidal neurons to detect morphological and functional synaptic alterations induced by 27-OH high levels. Our results show that elevated 27-OH levels lead to enhanced LTP in the Schaffer collateral-CA1 synapses. This increase is correlated with abnormally large dendritic spines in the stratum radiatum. Using immunohistochemistry for synaptopodin (actin-binding protein involved in the recruitment of the spine apparatus), we found a significantly higher density of synaptopodin-positive puncta in CA1 in Cyp27Tg mice. We hypothesize that high 27-OH levels alter synaptic potentiation and could lead to dysfunction of fine-tuned processing of information in hippocampal circuits resulting in cognitive impairment. We suggest that these alterations could be detrimental for synaptic function and cognition later in life, representing a potential mechanism by which hypercholesterolemia could lead to alterations in memory function in neurodegenerative diseases.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据