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Hydroxyurea attenuates oxidative, metabolic, and excitotoxic stress in rat hippocampal neurons and improves spatial memory in a mouse model of Alzheimer’s disease

ABSTRACT: Hydroxyurea attenuates oxidative, metabolic, and excitotoxic stress in rat hippocampal neurons and improves spatial memory in a mouse model of Alzheimer’s disease

PROVIDER: PRJNA438652 | ENA |

REPOSITORIES: ENA

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Hydroxyurea protects hippocampal neurons against oxidative, metabolic and excitotoxic stress, and improves spatial memory in a mouse model of Alzheimer’s disease (Rat)

Project description: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.

2018-09-10 | GSE111941 | GEO

Hydroxyurea protects hippocampal neurons against oxidative, metabolic and excitotoxic stress, and improves spatial memory in a mouse model of Alzheimer’s disease (Mouse)

2018-09-10 | GSE111940 | GEO

Hydroxyurea attenuates oxidative, metabolic, and excitotoxic stress in rat hippocampal neurons and improves spatial memory in a mouse model of Alzheimer’s disease

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-09-10 | GSE111943 | GEO

Hydroxyurea protects hippocampal neurons against oxidative, metabolic and excitotoxic stress, and improves spatial memory in a mouse model of Alzheimer’s disease (Mouse)

Project description:Hydroxyurea protects hippocampal neurons against oxidative, metabolic and excitotoxic stress, and improves spatial memory in a mouse model of Alzheimer’s disease (Mouse)

| PRJNA438664 | ENA

Hydroxyurea protects hippocampal neurons against oxidative, metabolic and excitotoxic stress, and improves spatial memory in a mouse model of Alzheimer’s disease (Rat)

Project description:Hydroxyurea protects hippocampal neurons against oxidative, metabolic and excitotoxic stress, and improves spatial memory in a mouse model of Alzheimer’s disease (Rat)

| PRJNA438665 | ENA

Hydroxyurea attenuates oxidative, metabolic, and excitotoxic stress in rat hippocampal neurons and improves spatial memory in a mouse model of Alzheimer's disease.

Project description: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 tested if hydroxyurea (HU), a ribonucleotide reductase inhibitor known to activate adaptive cellular stress responses and ameliorate abnormalities associated with several genetic disorders, could protect rat hippocampal neurons against oxidative-, excitatory-, mitochondrial-, and Aβ-induced stress and if HU treatment could improve learning and memory in the APP/PS1 mouse model of AD. HU treatment attenuated the loss of cell viability induced by treatment of hippocampal neurons with hydrogen peroxide, glutamate, rotenone, and Aβ1-42. HU treatment attenuated reductions of mitochondrial reserve capacity, maximal respiration, and cellular adenosine triphosphate content induced by hydrogen peroxide treatment. In vivo, treatment of APP/PS1 mice with HU (45 mg/kg/d) improved spatial memory performance in the hippocampus-dependent Morris water maze task without reducing Aβ levels. HU provides neuroprotection against toxic insults including Aβ, improves mitochondrial bioenergetics, and improves spatial memory in an AD mouse model. HU may offer a new therapeutic approach to delay cognitive decline in AD.

| S-EPMC6215724 | biostudies-literature

Oxidative Stress Mechanisms of Hydroxyurea-Induced Developmetal Toxicity in Organogenesis Stage Mouse Embryos

Project description:To investigate the gene expression changes in gestational day 9 embryos exposed to hydroxyurea in utero. Agilent microarray technology was used to identify genes that responded to hydroxyurea exposure. Understanding the stress response of the embryo will help us advance education of birth defect prevention. Gestational day 9 embryos were exposed to 400 mg/kg hydroxyurea, a dose that induces a moderate number of malformations, including fetal resorptions, growth retardation, external and skeletal defects. We identified several genes involved in responding to oxidative stress, including NRF-2, PRDX1, and TXNIP. Other genes also significantly changed were involved in cell cycle arrest and apoptosis. The dysregulation in gene expression during organogenesis contributes to the developmental toxicity of hydroxyurea. Gestational day 9 mouse embryos were treated with saline or 400 mg/kg hydroxyurea by intraperitoneal injection. Dams were euthanized after 3 hours and embryos explanted. 6 indendent experiments were performed for each sample.

2015-01-15 | E-GEOD-54579 | biostudies-arrayexpress

Tn-seq of hydroxyurea treated Bacillus subtilis cells

Project description:Hydroxyurea (HU) is thought to primarily target ribonucleotide reductase (RNR), therefore inhibiting the conversion of rNTPs into dNTPs and slowing DNA replication. To understand how Bacillus subtilis responds to HU stress, we performed RNA-seq and Tn-seq. We obtained genes with fitness defects following hydroxyurea treatment over 3 growth periods.

2021-03-29 | GSE169564 | GEO

Multicenter Study of Hydroxyurea (MSH)

Project description:Multicenter Study of Hydroxyurea (MSH)

| PRJNA701326 | ENA

Multicenter Study of Hydroxyurea (MSH)

Project description:Multicenter Study of Hydroxyurea (MSH)

| PRJNA701327 | ENA