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| Status |
Public on May 07, 2024 |
| Title |
Selective targeting and modulation of plaque associated microglia via systemic hydroxyl dendrimer administration in an Alzheimer’s disease mouse model. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: In Alzheimer’s disease (AD), microglia surround extracellular plaques and mount a sustained inflammatory response, contributing to the pathogenesis of the disease. Identifying approaches to specifically target plaque-associated microglia (PAMs) without interfering in the homeostatic functions of non-plaque associated microglia would afford a powerful tool and potential therapeutic avenue. Methods: Here, we demonstrated that a systemically administered nanomedicine, hydroxyl dendrimers (HDs), can cross the blood brain barrier and are preferentially taken up by PAMs in a mouse model of AD. As proof of principle, to demonstrate biological effects in PAM function, we treated the 5xFAD mouse model of amyloidosis for 4 weeks via systemic administration (ip, 2x weekly) of HDs conjugated to a colony stimulating factor-1 receptor (CSF1R) inhibitor (D-45113). Results: Treatment resulted in significant reductions in amyloid-beta (Aβ) and a stark reduction in the number of microglia and microglia-plaque association in the subiculum and somatosensory cortex, as well as a downregulation in microglial, inflammatory, and synaptic gene expression compared to vehicle treated 5xFAD mice. Conclusions: This study demonstrates that systemic administration of a dendranib may be utilized to target and modulate PAMs.
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| Overall design |
We took 12-month old WT, WT/D45113, 5xFAD, and 5xFAD/D45113 mice and performed bulk RNA Sequencing on the hippocampi to assess the differences in gene expression between each group
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| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
May 02, 2024 |
| Last update date |
May 07, 2024 |
| Contact name |
Kim Green |
| E-mail(s) |
kngreen@uci.edu
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| Organization name |
University of California, Irvine
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| Lab |
Green Lab
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| Street address |
3400 Biological Sciences III
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| City |
Irvine |
| State/province |
CA |
| ZIP/Postal code |
92617 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (32)
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| GSM8247702 |
Hippocampus, 5xFAD, D45113, 4F |
| GSM8247703 |
Hippocampus, 5xFAD, D45113, 1M |
| GSM8247704 |
Hippocampus, 5xFAD, D45113, 2M |
| GSM8247705 |
Hippocampus, 5xFAD, D45113, 3M |
| GSM8247706 |
Hippocampus, 5xFAD, D45113, 4M |
| GSM8247707 |
Hippocampus, WT, D45113, 1F |
| GSM8247708 |
Hippocampus, WT, D45113, 2F |
| GSM8247709 |
Hippocampus, WT, D45113, 3F |
| GSM8247710 |
Hippocampus, WT, D45113, 4F |
| GSM8247711 |
Hippocampus, WT, D45113, 1M |
| GSM8247712 |
Hippocampus, WT, D45113, 2M |
| GSM8247713 |
Hippocampus, WT, D45113, 3M |
| GSM8247714 |
Hippocampus, WT, D45113, 4M |
| GSM8247715 |
Hippocampus, 5xFAD, Vehicle, 1F |
| GSM8247716 |
Hippocampus, 5xFAD, Vehicle, 2F |
| GSM8247717 |
Hippocampus, 5xFAD, Vehicle, 3F |
| GSM8247718 |
Hippocampus, 5xFAD, Vehicle, 4F |
| GSM8247719 |
Hippocampus, 5xFAD, Vehicle, 1M |
| GSM8247720 |
Hippocampus, 5xFAD, Vehicle, 2M |
| GSM8247721 |
Hippocampus, 5xFAD, Vehicle, 3M |
| GSM8247722 |
Hippocampus, 5xFAD, Vehicle, 4M |
| GSM8247723 |
Hippocampus, WT, Vehicle, 1F |
| GSM8247724 |
Hippocampus, WT, Vehicle, 2F |
| GSM8247725 |
Hippocampus, WT, Vehicle, 3F |
| GSM8247726 |
Hippocampus, WT, Vehicle, 4F |
| GSM8247727 |
Hippocampus, WT, Vehicle, 1M |
| GSM8247728 |
Hippocampus, WT, Vehicle, 2M |
| GSM8247729 |
Hippocampus, WT, Vehicle, 3M |
| GSM8247730 |
Hippocampus, WT, Vehicle, 4M |
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| Relations |
| BioProject |
PRJNA1107236 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE266470_gene_fpkm_individual.xlsx |
17.2 Mb |
(ftp)(http) |
XLSX |
| GSE266470_gene_raw_count_individual.xlsx |
11.2 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
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