GSE111940 Hydroxyurea protects hippocampal neurons against oxidative, metabolic and excitotoxic stress, and improves spatial memory in a mouse model of Alzheimer ’s disease (Mouse)

Contributors : Rebecca D Brose ; Elin Lehrmann ; Yongqing Zhang ; Kirby D Smith ; Mark P MattsonSeries Type : Expression profiling by arrayOrganism : Mus musculusAlzheimer ’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 cellu lar 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.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Mus musculus Source Type: research