Guanosine Prevents Spatial Memory Impairment and Hippocampal Damage Following Amyloid-β1-42 Administration in Mice

Alzheimer's disease (AD) is a progressive neurodegenerative illness responsible for cognitive impairment and dementia. Accumulation of amyloid-beta (A beta) peptides in neurons and synapses causes cell metabolism to unbalance, and the production of reactive oxygen species (ROS), leading to neuronal death and cognitive damage. Guanosine is an endogenous nucleoside recognized as a neuroprotective agent since it prevents glutamate-induced neurotoxicity by a mechanism not yet completely elucidated. In this study, we evaluated behavioral and biochemical effects in the hippocampus caused by the intracerebroventricular (i.c.v.) infusion of A beta(1-42) peptide (400 pmol/site) in mice, and the neuroprotective effect of guanosine (8 mg/kg, i.p.). An initial evaluation on the eighth day after A beta(1-42) infusion showed no changes in the tail suspension test, although ex vivo analyses in hippocampal slices showed increased ROS production. In the second protocol, on the tenth day following A beta(1-42) infusion, no effect was observed in the sucrose splash test, but a reduction in the recognition index in the object location test showed impaired spatial memory. Analysis of hippocampal slices showed no ROS production and mitochondrial membrane potential alteration, but a tendency to increase glutamate release and a significant lactate release, pointing to a metabolic alteration. Those effects were accompanied by decreased cell viability and increased membrane damage. Guanosine treatment prevented behavioral and biochemical alterations evoked by A beta(1-42), suggesting a potential role against behavioral and biochemical damage evoked by A beta in the hippocampus.

Automated summary

Alzheimer's disease is a progressive neurodegenerative illness that causes cognitive impairment and dementia. Guanosine has been shown to prevent behavioral and biochemical alterations evoked by A beta, suggesting a potential role against damage caused by A beta in the hippocampus.