Involvement of GAT2/BGT-1 in the preventive effects of betaine on cognitive impairment and brain oxidative stress in amyloid β peptide-injected mice

Abstract Aging of mammalian species results in impaired biological function and cognitive decline. The purpose of this study was to determine the capacity of whey supplementation to improve aging –related changes of cognitive impairment markers; tau and amyloid-B and α-amylase in the brain of old rats. These have been conducted in conjunction with histopathology, immunohistochemistry and flow cytometry of apoptosis. Twenty-four male Wistar albino rats (Rattus novergicus) ages 8 and 30-M (months) old were used. They were arranged into four main groups; adult (8-month old) and old rats (30 month old) with or without buffalo whey syrup supplementation. Oral whey supplementations was given daily twice doses of 2 mL3 of whey syrup for two months. At the end of experiment, the rats were sacrificed by light anesthesia. The brain was examined for histological, immunohistochemical of synaptophysin and caspase 3 and biochemical and flow cytometric investigation. Old rats presented with depletion of superoxide dismutase (SOD), adenosine triphosphatase (ATP), dopamine (DA) and serotonin (5-HT). The 30 M old rats also presented with increased lipid peroxidation MDA, inflammatory markers (tumor necrosis factor- α and 5-lpooxygenase), apoptic marker caspase 3, Annexin-v and aging marker tau-protein, amyloid-β and α-amylase. The combination of these findings in old rats predicts cognitive impairment. Among old rats, whey supplementations reduced inflammatory and oxidative stress markers. Whey supplementation also enhanced neurotransmitters and decreased tau-protein, amyloid-β, α- amylase cognitive impairment markers. Improved the histopathology and immunohistochemistry of cerebrum, cerebellum and hippocampus of old rats confirmed these effects of supplementation. The rates of apoptosis were decreased by assessment of Annexin v via flow cytometry. Whey supplementation to 8M old rats resulted in maintenance of the brain structure and function. The authors concluded that whey contains antioxidants and amino acids that decrease brain oxidative stress and restore normal cognitive function. These findings were evaluated by enhanced antioxidant defense and DA and 5-HT neurotransmitters which coincides with improved histology. The authors concluded that whey contains antioxidants and amino acids that decrease brain oxidative stress and restore normal cognitive function. These findings were evaluated by enhanced antioxidant defense and DA and 5-HT neurotransmitters which coincides with improved histology.

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Roles of amyloid β-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimer's disease and mild cognitive impairment

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2007.05.037 ◽

2007 ◽

Vol 43 (5) ◽

pp. 658-677 ◽

Cited By ~ 356

Author(s):

D. Allan Butterfield ◽

Tanea Reed ◽

Shelley F. Newman ◽

Rukhsana Sultana

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Amyloid Β ◽

Amyloid Β Peptide ◽

Brain Protein ◽

Protein Modifications

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Lethal weapon: amyloid β-peptide, role in the oxidative stress and neurodegeneration of Alzheimer’s disease

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2004.02.002 ◽

2004 ◽

Vol 25 (5) ◽

pp. 581-587 ◽

Cited By ~ 13

Author(s):

Debomoy K Lahiri ◽

Nigel H Greig

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Β ◽

Amyloid Β Peptide

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Feasibility of 3-month melatonin supplementation for brain oxidative stress and sleep in mild cognitive impairment: protocol for a randomised, placebo-controlled study

BMJ Open ◽

10.1136/bmjopen-2020-041500 ◽

2021 ◽

Vol 11 (2) ◽

pp. e041500

Author(s):

Zoe Menczel Schrire ◽

Craig L Phillips ◽

Shantel L Duffy ◽

Nathaniel S Marshall ◽

Loren Mowszowski ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Randomised Controlled Trial ◽

Controlled Trial ◽

Feasibility Trial ◽

Controlled Study ◽

Brain Oxidative Stress ◽

Randomised Controlled

IntroductionMelatonin has multiple proposed therapeutic benefits including antioxidant properties, synchronisation of the circadian system and lowering of blood pressure. In this protocol, we outline a randomised controlled trial to assess the feasibility, acceptability and tolerability of higher dose (25 mg) melatonin to target brain oxidative stress and sleep disturbance in older adults with mild cognitive impairment (MCI).Methods and analysisThe study design is a randomised double-blind, placebo-controlled, parallel group trial. Forty individuals with MCI will be recruited from the Healthy Brain Ageing Clinic, University of Sydney and from the community, and randomised to receive either 25 mg oral melatonin or placebo nightly for 12 weeks. The primary outcomes are feasibility of recruitment, acceptability of intervention and adherence to trial medication at 12 weeks. Secondary outcomes will include the effect of melatonin on brain oxidative stress as measured by magnetic resonance spectroscopy, blood pressure, blood biomarkers, mood, cognition and sleep. Outcomes will be collected at 6 and 12 weeks. The results of this feasibility trial will inform a future conclusive randomised controlled trial to specifically test the efficacy of melatonin on modifiable risk factors of dementia, as well as cognition and brain function. This will be the first trial to investigate the effect of melatonin in the population with MCI in this way, with the future aim of using this approach to reduce progression to dementia.Ethics and disseminationThis protocol has been approved by the Sydney Local Health District Ethics Committee (X18-0077). This randomised controlled trial will be conducted in compliance with the protocol published in the registry, the International Conference for Harmonisation on Good Clinical Practice and all other applicable regulatory requirements. The findings of the trial will be disseminated via conferences, publications and media, as applicable. Participants will be informed of results of the study at the conclusion of the trial. Eligible authors will include investigators who are involved in the conception and design of the study, the conduct of the trial, the analysis of the results, and reporting and presentation of study findings.Trial registration numberAustralian and New Zealand Clinical Trials Registry (ANZCTRN 12619000876190).Protocol versionV.8 15 October 2020.

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Effects of Folic Acid Combined with DHA Supplementation on Cognitive Function and Amyloid-β-Related Biomarkers in Older Adults with Mild Cognitive Impairment by a Randomized, Double Blind, Placebo-Controlled Trial

Journal of Alzheimer s Disease ◽

10.3233/jad-200997 ◽

2021 ◽

pp. 1-13

Author(s):

Dong Bai ◽

Junting Fan ◽

Mengyue Li ◽

Cuixia Dong ◽

Yiming Gao ◽

...

Keyword(s):

Cognitive Impairment ◽

Folic Acid ◽

Mild Cognitive Impairment ◽

Cognitive Function ◽

Digit Span ◽

Controlled Trial ◽

Amyloid Β ◽

Amyloid Β Peptide ◽

Double Blind ◽

Full Scale Intelligence Quotient

Background: The neuroprotective benefits of combined folic acid and docosahexaenoic acid (DHA) on cognitive function in mild cognitive impairment (MCI) patients are suggested but unconfirmed. Objective: To explore the effects of 6-month folic acid + DHA on cognitive function in patients with MCI. Methods: Our randomized controlled trial (trial number ChiCTR-IOR-16008351) was conducted in Tianjin, China. We divided 160 MCI patients aged > 60 years into four regimen groups randomly: folic acid (0.8 mg/day) + DHA (800 mg/day), folic acid (0.8 mg/day), DHA (800 mg/day), and placebo, for 6 months. Cognitive function and blood amyloid-β peptide (Aβ) biomarker levels were measured at baseline and 6 months. Cognitive function was also measured at 12 months. Results: A total of 138 patients completed this trial. Folic acid improved the full-scale intelligence quotient (FSIQ), arithmetic, and picture complement scores; DHA improved the FSIQ, information, arithmetic, and digit span scores; folic acid + DHA improved the arithmetic (difference 1.67, 95% CI 1.02 to 2.31) and digital span (1.33, 0.24 to 2.43) scores compared to placebo. At 12 months, all scores declined in the intervention groups. Folic acid and folic acid + DHA increased blood folate (folic acid + DHA: 7.70, 3.81 to 11.59) and S-adenosylmethionine (23.93, 1.86 to 46.00) levels and reduced homocysteine levels (–6.51, –10.57 to –2.45) compared to placebo. DHA lower the Aβ40 levels (–40.57, –79.79 to –1.35) compared to placebo (p < 0.05), and folic acid + DHA reduced the Aβ42 (–95.59, –150.76 to –40.43) and Aβ40 levels (–45.75, –84.67 to –6.84) more than DHA (p < 0.05). Conclusion: Folic acid and DHA improve cognitive function and reduce blood Aβ production in MCI patients. Combination therapy may be more beneficial in reducing blood Aβ-related biomarkers.

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