| Autor: |
da Silva JS; Graduate Program in Biological Sciences - Biochemistry. Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul - UFRGS, Porto Alegre, Brazil., Nonose Y; Graduate Program in Biological Sciences - Biochemistry. Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul - UFRGS, Porto Alegre, Brazil., Rohden F; Graduate Program in Biological Sciences - Biochemistry. Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul - UFRGS, Porto Alegre, Brazil., Lukasewicz Ferreira PC; Graduate Program in Biological Sciences - Biochemistry. Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul - UFRGS, Porto Alegre, Brazil., Fontella FU; Graduate Program in Biological Sciences - Biochemistry. Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul - UFRGS, Porto Alegre, Brazil., Rocha A; Graduate Program in Biological Sciences - Biochemistry. Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul - UFRGS, Porto Alegre, Brazil., Brochier AW; Graduate Program in Biological Sciences - Biochemistry. Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul - UFRGS, Porto Alegre, Brazil., Apel RV; Graduate Program in Biological Sciences - Biochemistry. Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul - UFRGS, Porto Alegre, Brazil., de Lima TM; Graduate Program in Biological Sciences - Biochemistry. Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul - UFRGS, Porto Alegre, Brazil., Seminotti B; Graduate Program in Biological Sciences - Biochemistry. Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul - UFRGS, Porto Alegre, Brazil., Amaral AU; Graduate Program in Biological Sciences - Biochemistry. Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul - UFRGS, Porto Alegre, Brazil.; Department of Biological Sciences, Integrated Regional University of High Uruguay and Missions - URI, Erechim, Brazil., Galina A; Laboratory of Bioenergetics and Mitochondrial Physiology. Graduate Program in Cellular Biophysics and Biochemistry. Institute of Medical Biochemistry Leopoldo de Meis, Health Sciences Centre, Federal University of Rio de Janeiro - UFRJ, Rio de Janeiro, Brazil., Souza DO; Graduate Program in Biological Sciences - Biochemistry. Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul - UFRGS, Porto Alegre, Brazil. diogo.bioq@gmail.com. |
| Abstrakt: |
Amyloid-β oligomers (AβOs) toxicity causes mitochondrial dysfunction, leading to synaptic failure in Alzheimer's disease (AD). Considering presynaptic high energy demand and tight Ca 2+ 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 Ca 2+ handling, and caused mitochondrial swelling in hippocampal synaptosomes. Guanosine crossed the BBB, recovered OR short-term memory, reestablished glutamate uptake, recovered mitochondrial Ca 2+ 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. |
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