Inosine protects against impairment of memory induced by experimental model of Alzheimer disease: a nucleoside with multitarget brain actions

Teixeira, Fernanda Cardoso; Gutierres, Jessié Martins; Soares, Mayara Sandrielly Pereira; Mattos, Bruna da Siveira de; Spohr, Luíza; Couto, Carlus Augustu Tavares do; Bona, Natália Pontes; Assmann, Charles Elias; Morsch, Vera Maria; Cruz, Ivana Beatrice Mânica da; Stefanello, Francieli Moro; Spanevello, Rosélia Maria

doi:10.1007/s00213-019-05419-5

Cited by 37 publications

(28 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, inosine increased the serum levels of uric acid, a potent natural antioxidant. Teixeira et al (2020) also demonstrated that inosine prevented an increase in Na + /K + -ATPase and Mg-ATPase activities and decreased Ca 2+ -ATPase activity in the hippocampus and cerebral cortex induced by STZ. These actions on ion pumps can be related to the antioxidant effects of inosine and neurotransmitter release.…”

Section: Inosine and Cognitionmentioning

confidence: 79%

“…Animal models of Alzheimer’s disease (AD) have also been used to study the effects of inosine. In one study, AD was induced by streptozotocin (STZ), and the animals received inosine by intracerebroventricular route for 25 days ( Teixeira et al, 2020 ). It is well demonstrated that administration of STZ in the brain induces changes similar to those found in AD such as learning and memory deficit, mitochondrial abnormalities, oxidative stress, neuronal cell damage and brain glucose metabolism alterations ( Teixeira et al, 2020 ).…”

Section: Inosine and Cognitionmentioning

confidence: 99%

“…In one study, AD was induced by streptozotocin (STZ), and the animals received inosine by intracerebroventricular route for 25 days ( Teixeira et al, 2020 ). It is well demonstrated that administration of STZ in the brain induces changes similar to those found in AD such as learning and memory deficit, mitochondrial abnormalities, oxidative stress, neuronal cell damage and brain glucose metabolism alterations ( Teixeira et al, 2020 ). This study demonstrated that inosine prevented memory deficits in the inhibitory avoidance task and the Y-maze test ( Teixeira et al, 2020 ).…”

Section: Inosine and Cognitionmentioning

confidence: 99%

“…It is well demonstrated that administration of STZ in the brain induces changes similar to those found in AD such as learning and memory deficit, mitochondrial abnormalities, oxidative stress, neuronal cell damage and brain glucose metabolism alterations ( Teixeira et al, 2020 ). This study demonstrated that inosine prevented memory deficits in the inhibitory avoidance task and the Y-maze test ( Teixeira et al, 2020 ). In addition, inosine increased the serum levels of uric acid, a potent natural antioxidant.…”

Section: Inosine and Cognitionmentioning

confidence: 99%

See 3 more Smart Citations

Inosine as a Tool to Understand and Treat Central Nervous System Disorders: A Neglected Actor?

Nascimento

Macedo-Júnior²,

Lapa-Costa

et al. 2021

Front. Neurosci.

View full text Add to dashboard Cite

Since the 1970s, when ATP was identified as a co-transmitter in sympathetic and parasympathetic nerves, it and its active metabolite adenosine have been considered relevant signaling molecules in biological and pathological processes in the central nervous system (CNS). Meanwhile, inosine, a naturally occurring purine nucleoside formed by adenosine breakdown, was considered an inert adenosine metabolite and remained a neglected actor on the purinergic signaling scene in the CNS. However, this scenario began to change in the 1980s. In the last four decades, an extensive group of shreds of evidence has supported the importance of mediated effects by inosine in the CNS. Also, inosine was identified as a natural trigger of adenosine receptors. This evidence has shed light on the therapeutic potential of inosine on disease processes involved in neurological and psychiatric disorders. Here, we highlight the clinical and preclinical studies investigating the involvement of inosine in chronic pain, schizophrenia, epilepsy, depression, anxiety, and in neural regeneration and neurodegenerative diseases, such as Parkinson and Alzheimer. Thus, we hope that this review will strengthen the knowledge and stimulate more studies about the effects promoted by inosine in neurological and psychiatric disorders.

show abstract

Section: Inosine and Cognitionmentioning

confidence: 79%

Section: Inosine and Cognitionmentioning

confidence: 99%

Section: Inosine and Cognitionmentioning

confidence: 99%

Section: Inosine and Cognitionmentioning

confidence: 99%

See 2 more Smart Citations

Inosine as a Tool to Understand and Treat Central Nervous System Disorders: A Neglected Actor?

Nascimento

Macedo-Júnior²,

Lapa-Costa

et al. 2021

Front. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The most notable changes in individual metabolites involved in purine metabolism following CAW treatment were inosine and hypoxanthine, both of which were significantly decreased in 5xFAD males and 5xFAD females. Inosine, a purine nucleoside produced through the catabolism of adenosine ( Teixeira et al, 2020 ), is increased in various animal models of AD ( González-Domínguez et al, 2014 ; González-Domínguez et al, 2015 ; Esteve et al, 2017 ) and in several brain regions in post-mortem brain samples from patients with AD. ( Alonso-Andrés et al, 2018 ) This suggests that CAW may act by normalizing inosine levels, though inosine was not elevated in untreated male and female 5xFAD mice in this study.…”

Section: Discussionmentioning

confidence: 99%

Centella asiatica Alters Metabolic Pathways Associated With Alzheimer’s Disease in the 5xFAD Mouse Model of ß-Amyloid Accumulation

et al. 2021

View full text Add to dashboard Cite

Centella asiatica is an herb used in Ayurvedic and traditional Chinese medicine for its beneficial effects on brain health and cognition. Our group has previously shown that a water extract of Centella asiatica (CAW) elicits cognitive-enhancing effects in animal models of aging and Alzheimer’s disease, including a dose-related effect of CAW on memory in the 5xFAD mouse model of ß-amyloid accumulation. Here, we endeavor to elucidate the mechanisms underlying the effects of CAW in the brain by conducting a metabolomic analysis of cortical tissue from 5xFAD mice treated with increasing concentrations of CAW. Tissue was collected from 8-month-old male and female 5xFAD mice and their wild-type littermates treated with CAW (0, 200, 500, or 1,000 mg/kg/d) dissolved in their drinking water for 5 weeks. High-performance liquid chromatography coupled to high-resolution mass spectrometry analysis was performed and relative levels of 120 annotated metabolites were assessed in the treatment groups. Metabolomic analysis revealed sex differences in the effect of the 5xFAD genotype on metabolite levels compared to wild-type mice, and variations in the metabolomic response to CAW depending on sex, genotype, and CAW dose. In at least three of the four treated groups (5xFAD or wild-type, male or female), CAW (500 mg/kg/d) significantly altered metabolic pathways related to purine metabolism, nicotinate and nicotinamide metabolism, and glycerophospholipid metabolism. The results are in line with some of our previous findings regarding specific mechanisms of action of CAW (e.g., improving mitochondrial function, reducing oxidative stress, and increasing synaptic density). Furthermore, these findings provide new information about additional, potential mechanisms for the cognitive-enhancing effect of CAW, including upregulation of nicotinamide adenine dinucleotide in the brain and modulation of brain-derived neurotrophic factor. These metabolic pathways have been implicated in the pathophysiology of Alzheimer’s disease, highlighting the therapeutic potential of CAW in this neurodegenerative disease.

show abstract

Neuroprotection elicited by taurine in sporadic Alzheimer-like disease: benefits on memory and control of neuroinflammation in the hippocampus of rats

Huf,

Gutierres,

da Silva

et al. 2023

Mol Cell Biochem

View full text Add to dashboard Cite

Inosine protects against impairment of memory induced by experimental model of Alzheimer disease: a nucleoside with multitarget brain actions

Cited by 37 publications

References 61 publications

Inosine as a Tool to Understand and Treat Central Nervous System Disorders: A Neglected Actor?

Inosine as a Tool to Understand and Treat Central Nervous System Disorders: A Neglected Actor?

Centella asiatica Alters Metabolic Pathways Associated With Alzheimer’s Disease in the 5xFAD Mouse Model of ß-Amyloid Accumulation

Neuroprotection elicited by taurine in sporadic Alzheimer-like disease: benefits on memory and control of neuroinflammation in the hippocampus of rats

Contact Info

Product

Resources

About