Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease

Resende, Rosa; Moreira, Paula I.; Proença, Teresa; Deshpande, Atul; Busciglio, Jorge; Pereira, Cláudia; Oliveira, Catarina R.

doi:10.1016/j.freeradbiomed.2008.03.012

Cited by 301 publications

(204 citation statements)

References 60 publications

Supporting

Mentioning

190

Contrasting

Order By: Relevance

“…In 3xTg-AD mice, vitamin E and glutathione, two non-enzymatic antioxidants, were shown to be decreased and the levels of several lipid peroxidation markers were increased before the appearance of A␤ plaques and neurofibrillary tangles (Resende et al, 2008). In the current study, we found that L-NBP significantly reduced the level of lipid peroxidation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

L-3-n-Butylphthalide Improves Cognitive Impairment and Reduces Amyloid- in a Transgenic Model of Alzheimer's Disease

Peng¹,

Sun²,

Hon³

et al. 2010

Journal of Neuroscience

124

View full text Add to dashboard Cite

Alzheimer's disease (AD) is an age-related, progressive neurodegenerative disorder that occurs gradually and results in memory, behavior, and personality changes. L-3-n-butylphthalide (L-NBP), an extract from seeds of Apium graveolens Linn (Chinese celery), has been demonstrated to have neuroprotective effects on ischemic, vascular dementia, and amyloid-␤ (A␤)-infused animal models. In the current study, we examined the effects of L-NBP on learning and memory in a triple-transgenic AD mouse model (3xTg-AD) that develops both plaques and tangles with aging, as well as cognitive deficits. Ten-month-old 3xTg-AD mice were given 15 mg/kg L-NBP by oral gavage for 18 weeks. L-NBP treatment significantly improved learning deficits, as well as long-term spatial memory, compared with vehicle control treatment. L-NBP treatment significantly reduced total cerebral A␤ plaque deposition and lowered A␤ levels in brain homogenates but had no effect on fibrillar A␤ plaques, suggesting preferential removal of diffuse A␤ deposits. Furthermore, we found that L-NBP markedly enhanced soluble amyloid precursor protein secretion (␣APPs), ␣-secretase, and PKC␣ expression but had no effect on steady-state full-length APP. Thus, L-NBP may direct APP processing toward a non-amyloidogenic pathway and preclude A␤ formation in the 3xTg-AD mice. The effect of L-NBP on regulating APP processing was further confirmed in neuroblastoma SK-N-SH cells overexpressing wild-type human APP 695 (SK-N-SH APPwt). L-NBP treatment in 3xTg-AD mice also reduced glial activation and oxidative stress compared with control treatment. L-NBP shows promising preclinical potential as a multitarget drug for the prevention and/or treatment of Alzheimer's disease.

show abstract

Section: Discussionmentioning

confidence: 99%

“…In the 3xTg AD mouse model, it had been demonstrated that oxidative stress occurs at an early stage, before the appearance of A␤ plaques and neurofibrillary tangles (Resende et al, 2008). MDA, a lipid peroxidation end product, is an indicator of oxidative stress (Jackson, 1999).…”

Section: L-nbp Decreased Oxidative Stress In 3xtg-ad Micementioning

confidence: 99%

L-3-n-Butylphthalide Improves Cognitive Impairment and Reduces Amyloid- in a Transgenic Model of Alzheimer's Disease

Peng¹,

Sun²,

Hon³

et al. 2010

Journal of Neuroscience

124

View full text Add to dashboard Cite

show abstract

“…Since FR were accused as causal factors in a large number of diseases, these were sometimes referred as ''Free Radical Diseases''. Some of the important diseases and health issues in this category are cancer [61][62][63][64][65][66][67], cardiovascular diseases [68][69][70][71][72][73], atherosclerosis [74][75][76][77][78][79][80][81], neurological disorders [82][83][84][85][86], renal disorders [87][88][89][90], liver disorders [91][92][93], hypertension [50,94,95], rheumatoid arthritis [96,97], adult respiratory distress syndrome, auto-immune deficiency diseases [98,99], inflammation, degenerative disorders associated with aging [100][101][102][103], diabetes mellitus [104][105]…”

Section: Reactive Oxygen Species and Reactive Nitrogen Species Transimentioning

confidence: 99%

Reconvene and Reconnect the Antioxidant Hypothesis in Human Health and Disease

Singh

Chandra

Mahdi

et al. 2010

Indian J Clin Biochem

View full text Add to dashboard Cite

The antioxidants are essential molecules in human system but are not miracle molecules. They are neither performance enhancers nor can prevent or cure diseases when taken in excess. Their supplemental value is debateable. In fact, many high quality clinical trials on antioxidant supplement have shown no effect or adverse outcomes ranging from morbidity to all cause mortality. Several Chochrane Meta-analysis and Markov Model techniques, which are presently best available statistical models to derive conclusive answers for comparing large number of trials, support these claims. Nevertheless none of these statistical techniques are flawless. Hence, more efforts are needed to develop perfect statistical model to analyze the pooled data and further double blind, placebo controlled interventional clinical trials, which are gold standard, should be implicitly conducted to get explicit answers. Superoxide dismutase (SOD), glutathione peroxidase and catalase are termed as primary antioxidants as these scavenge superoxide anion and hydrogen peroxide. All these three enzymes are inducible enzymes, thereby inherently meaning that body increases or decreases their activity as per requirement. Hence there is no need to attempt to manipulate their activity nor have such efforts been clinically useful. SOD administration has been tried in some conditions especially in cancer and myocardial infarction but has largely failed, probably because SOD is a large molecule and can not cross cell membrane. The dietary antioxidants, including nutrient antioxidants are chain breaking antioxidants and in tandem with enzyme antioxidants temper the reactive oxygen species (ROS) and reactive nitrogen species (RNS) within physiological limits. Since body is able to regulate its own requirements of enzyme antioxidants, the diet must provide adequate quantity of non-enzymic antioxidants to meet the normal requirements and provide protection in exigent condition. So far, there is no evidence that human tissues ever experience the torrent of reactive species and that in chronic conditions with mildly enhanced generation of reactive species, the body can meet them squarely if antioxidants defense system in tissues is biochemically optimized. We are not yet certain about optimal levels of antioxidants in tissues. Two ways have been used to assess them: first by dietary intake and second by measuring plasma levels. Lately determination of plasma/serum level of antioxidants is considered better index for diagnostic and prognostic purposes. The recommended levels for vitamin A, E and C and beta carotene are 2.2-2.8 lmol/l; 27.5-30 lmol/l; 40-50 lmol/l and 0.4-0.5 lmol/l, respectively. The requirement and recommended blood levels of other dietary antioxidants are not established. The resolved issues are (1) essential to scavenge excess of radical species (2) participants in redox homeostasis (3) selective antioxidants activity against radical species (4) there is no universal antioxidant and 5) therapeutic value in case of deficiency. The overar...

show abstract

“…They involve a complex network of interconnected factors such as cholinergic dysfunction, aggregation and accumulation of β-amyloid (Aβ), intracellular formation of neurofibrillary tangles composed by tau, oxidative stress, neuronal loss, and so on. [5][6][7][8] A lot of reports have shown that brain-derived neurotrophic factor (BDNF) is critical for the establishment and maintenance of memory, while the dysfunction of BDNF system leads to memory impairments. 9,10) It is known that BDNF combines to tyrosine kinase receptor B (TrkB) in the cell membrane, and then inducing the activation of several intracellular signaling pathways.…”

mentioning

confidence: 99%

The Anti-dementia Effects of Donepezil Involve miR-206-3p in the Hippocampus and Cortex

Wang

et al. 2017

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a most serious age-related neurodegenerative disorder accompanied with significant memory impairments in this world. Recently, microRNAs (miRNAs) have been reported to be invlolved in the pathophysiology of AD. Previous studies have shown that miRNA-206 (miR-206) is implicated in the pathogenesis of AD via suppressing the expression of brain-derived neurotrophic factor (BDNF) in the brain. Here, we examined the miR-206-3p and miR-206-5p expression in the hippocampus and cortex of Abeta precursor protein (APP)/presenilin-1 (PS1) transgenic mice treated with donepezil, a drug approved for treating AD in clinic. We found that the expression of miR-206-3p was significantly up-regulated in the hippocampus and cortex of APP/PS1 mice, while donepezil administration significantly reversed this dysfunction. In addition, enhancing the miR-206-3p level by the usage of AgomiR-206-3p significantly attenuated the anti-dementia effects of donepezil in APP/PS1 mice. Together, these results suggested that miR-206-3p is involved in the anti-dementia effects of donepezil, and could be a novel pharmacological target for treating AD.Key words Alzheimer's disease; brain-derived neurotrophic factor; donepezil; microRNA (miRNA)-206-3pAlzheimer's disease (AD) is a serious neurodegenerative disorder in old people, and always accompanied with significant memory impairments, affecting mainly the hippocampus and frontal cortex. 1,2) AD patients display relatively slow, chronic but progressive neurodegeneration and memory impairments, ultimately leading to full dementia.3,4) Recent survey found that AD is responsible for about 50-60% of all cases of dementia in people over age 65. 3,4) The etiology of AD remains unclear, though many pathophysiologic hallmarks of this disease have been disclosed and are currently well established. They involve a complex network of interconnected factors such as cholinergic dysfunction, aggregation and accumulation of β-amyloid (Aβ), intracellular formation of neurofibrillary tangles composed by tau, oxidative stress, neuronal loss, and so on.5-8) A lot of reports have shown that brain-derived neurotrophic factor (BDNF) is critical for the establishment and maintenance of memory, while the dysfunction of BDNF system leads to memory impairments.9,10) It is known that BDNF combines to tyrosine kinase receptor B (TrkB) in the cell membrane, and then inducing the activation of several intracellular signaling pathways.11-13) Accumulating evidences have indicated that BDNF is implicated in the pathophysiology of AD. Previous studies have already found the reduced expression of BDNF in several brain regions (especially the hippocampus) of postmortem AD samples.14,15) By using the immunohistochemical method, Connor et al. found a significant reduction in not only intensity, but also the number of BDNF-immunoreactive cell in the hippocampus and cortex of AD samples.16) In addition, it was also thought that the Aβ-induced neurotoxicity and dendrite atrophy may due to a consequence of BDNF def...

show abstract

Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease

Cited by 301 publications

References 60 publications

L-3-n-Butylphthalide Improves Cognitive Impairment and Reduces Amyloid- in a Transgenic Model of Alzheimer's Disease

L-3-n-Butylphthalide Improves Cognitive Impairment and Reduces Amyloid- in a Transgenic Model of Alzheimer's Disease

Reconvene and Reconnect the Antioxidant Hypothesis in Human Health and Disease

The Anti-dementia Effects of Donepezil Involve miR-206-3p in the Hippocampus and Cortex

Contact Info

Product

Resources

About