Souza da Silva 2020 Mol Neurobiol
|Souza da Silva J, Nonose Y, Rohden F, Lukasewicz Ferreira PC, Fontella FU, Rocha A, Wigner Brochier A, Vieira Apel R, de Lima TM, Seminotti B, Amaral AU, Galina A, Souza DO (2020) Guanosine neuroprotection of presynaptic mitochondrial calcium homeostasis in a mouse study with amyloid-β oligomers. Mol Neurobiol 57:4790-809.|
Souza da Silva Jussemara, Nonose Yasmine, Rohden Francieli, Lukasewicz Ferreira Pamela C, Fontella Fernanda Urruth, Rocha Andreia, Wigner Brochier Andressa, Vieira Apel Rodrigo, de Lima Thais Martins, Seminotti Bianca, Umpierrez Amaral Alexandre, Galina Antonio, Souza Diogo O (2020) Mol Neurobiol
Abstract: Amyloid-β oligomers (AβOs) toxicity causes mitochondrial dysfunction, leading to synaptic failure in Alzheimer's disease (AD). Considering presynaptic high energy demand and tight Ca2+ regulation, impairment of mitochondrial function can lead to deteriorated neural activity and cell death. In this study, an AD mouse model induced by ICV (intracerebroventricular) injection of AβOs was used to investigate the toxicity of AβOs on presynaptic function. As a therapeutic approach, GUO (guanosine) was given by oral route to evaluate the neuroprotective effects on this AD model. Following 24 h and 48 h from the model induction, behavioral tasks and biochemical analyses were performed, respectively. AβOs impaired object recognition (OR) short-term memory and reduced glutamate uptake and oxidation in the hippocampus. Moreover, AβOs decreased spare respiratory capacity, reduced ATP levels, impaired Ca2+ handling, and caused mitochondrial swelling in hippocampal synaptosomes. Guanosine crossed the BBB, recovered OR short-term memory, reestablished glutamate uptake, recovered mitochondrial Ca2+ homeostasis, and partially prevented mitochondrial swelling. Therefore, this endogenous purine presented a neuroprotective effect on presynaptic mitochondria and should be considered for further studies in AD models.
• Keywords: Alzheimer’s disease, Amyloid-β oligomers, Guanosine, Neuroprotection, Presynaptic mitochondria • Bioblast editor: Plangger M • O2k-Network Lab: BR Rio de Janeiro Galina A, BR Rio de Janeiro Institute Biomedical Chemistry, BR Porto Alegre Souza DOG
Labels: MiParea: Respiration, Pharmacology;toxicology Pathology: Alzheimer's
Organism: Mouse Tissue;cell: Nervous system Preparation: Homogenate
Coupling state: LEAK, OXPHOS, ET Pathway: N, S, NS, ROX HRR: Oxygraph-2k, O2k-Fluorometer, Ca