Guanosine Neuroprotection of Presynaptic Mitochondrial Calcium Homeostasis in a Mouse Study with Amyloid-β Oligomers.

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.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

da Silva JS,Nonose Y,Rohden F,Lukasewicz Ferreira PC,Fontella FU,Rocha A,Brochier AW,Apel RV,de Lima TM,Seminotti B,Amaral AU,Galina A,Souza DO

doi

10.1007/s12035-020-02064-4

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

4790-4809

issue

11

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-020-02064-4

journal_volume

57

pub_type

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