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| Status |
Public on Sep 10, 2018 |
| Title |
Hydroxyurea protects hippocampal neurons against oxidative, metabolic and excitotoxic stress, and improves spatial memory in a mouse model of Alzheimer’s disease (Mouse) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Alzheimer’s disease (AD) is an age-related neurodegenerative disorder characterized by accumulation of amyloid β-peptide (Aβ) plaques in the brain and decreased cognitive function leading to dementia. We determined if hydroxyurea (HU), a ribonucleotide reductase inhibitor known to activate adaptive cellular stress responses in fibroblasts, could protect rat hippocampal neurons against oxidative-, excitatory-, mitochondrial-, and Aβ-induced stress and if HU treatment could improve learning and memory in a mouse model of AD (APP/PS1 double mutant transgenic mice). HU treatment attenuated the loss of cell viability induced by treatment of hippocampal neurons with hydrogen peroxide, glutamate, rotenone, and Aβ1-42. HU treatment also attenuated reductions of mitochondrial reserve capacity, maximal respiration, and cellular ATP content induced by hydrogen peroxide treatment. In vivo, treatment of APP/PS1 AD mice with HU (45 mg/kg/day) improved spatial memory performance in the hippocampus-dependent Morris water maze task. In summary, HU provides neuroprotection against toxic insults, improves mitochondrial bioenergetics, and improves spatial memory in a mouse model of AD. HU may offer a new therapeutic approach to delay cognitive decline in AD.
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| Overall design |
RNA extracted from hippocampi from four APP/PS1 mice nontransgenic control littermates treated with HU (45 mg/kg/day) for 2.5 months were compared to that of four untreated control animals.
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| Contributor(s) |
Brose RD, Lehrmann E, Zhang Y, Smith KD, Mattson MP |
| Citation(s) |
30245242 |
| Submission date |
Mar 16, 2018 |
| Last update date |
Jun 22, 2020 |
| Contact name |
Supriyo De |
| Organization name |
NIA-IRP, NIH
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| Department |
Laboratory of Genetics and Genomics
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| Lab |
Computational Biology & Genomics Core
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| Street address |
251 Bayview Blvd
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| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21224 |
| Country |
USA |
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| Platforms (1) |
| GPL13912 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE111943 |
Hydroxyurea attenuates oxidative, metabolic, and excitotoxic stress in rat hippocampal neurons and improves spatial memory in a mouse model of Alzheimer’s disease |
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| Relations |
| BioProject |
PRJNA438664 |
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