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

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative illness responsible for cognitive impairment and dementia. Accumulation of amyloid-beta (Aβ) 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 Aβ1-42 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 Aβ1-42 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 Aβ1-42 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 Aβ1-42, suggesting a potential role against behavioral and biochemical damage evoked by Aβ in the hippocampus.

Metabolomic analysis identifies guanosine as an early biomarker in Diabetic Cognitive Dysfunction in high-altitude

“…In summary, through an in-depth and comprehensive analysis of the serum metabolomics of T-T2DM and L-T2DM patients, we found that DMs mainly included pipecolic acid, lauric acid, guanosine and kaempferol and were mainly involved in lysine degradation, fatty acid biosynthesis, purine metabolism and metabolic pathways. Machine learning further identi ed guanosine as the most characteristic cognition-related metabolic biomarker for DCD in high-altitude, which is consistent with another study showing that guanosine can prevent spatial memory dysfunction and hippocampal damage after amyloid-beta administration in mice [31]. In addition, this study provides rst-hand evidence in diabetic with cognitive function in high-altitude.…”

Guanosine increases global SUMO1‐ylation in the hippocampus of young and aged mice and improves the short‐term memory of young mice

“…Guanosine displays anticonvulsant effect (De Oliveira et al, 2004), protective effect against ischemic conditions (Dal‐Cim et al, 2019; Hansel et al, 2015), and antidepressant‐like effects (Bettio et al, 2016). Also, guanosine has protective effects in AD rodent models (Coelho et al, 2022; Lanznaster et al, 2017; Pettifer et al, 2004), and improved mitochondrial function and ameliorated motor and cognitive behavior in rodent PD models (Marques et al, 2019) among others (Lanznaster et al, 2016; Massari et al, 2021; Schmidt et al, 2007). In addition, a potential anti‐aging effect of guanosine has been shown in glial cells (Souza et al, 2016).…”