Biochimica et biophysica acta
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Biochim. Biophys. Acta · Apr 2012
Hypoxic preconditioning increases iron transport rate in astrocytes.
The mechanisms involved in the neuroprotection induced by hypoxic preconditioning (HP) have not been fully elucidated. The involvement of hypoxia-inducible factor-1 alpha (HIF-1alpha) in such neuroprotection has been confirmed. There is also evidence showing that a series of genes with important functions in iron metabolism, including transferrin receptor (TfR1) and divalent metal transporter 1 (DMT1), are regulated by HIF-1alpha in response to hypoxia in extra-neural organs or cells. ⋯ We concluded that HP has the ability to increase iron transport speed in astrocytes. Based on our findings and the importance of astrocytes in neuronal survival in hypoxic/ischemic preconditioning, we proposed that the increase in iron transport rate and cellular iron in astocytes might be one of the mechanisms associated with the HP-induced neuroprotection. We also demonstrated that ferroportin1 expression was significantly affected by HIF-1alpha in astrocytes, implying that the gene encoding this iron efflux protein might be a hypoxia-inducible one.
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Biochim. Biophys. Acta · Apr 2012
Ginsenoside Rg1 promotes nonamyloidgenic cleavage of APP via estrogen receptor signaling to MAPK/ERK and PI3K/Akt.
The pathogenic accumulation of amyloid β peptide (Aβ), a natural occurring peptide processed from beta-amyloid precursor protein (APP), is considered to play a key role in the development of Alzheimer's disease (AD). Ginsenoside Rg1, an active component in ginseng, has been identified as a phytoestrogen and also found to be neuroprotective. However, it is unknown whether Rg1-induced estrogenic activity intervenes in APP processing, and improves memory performance. ⋯ Rg1 might be used to slow or prevent AD, in particular in postmenopausal females.
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Biochim. Biophys. Acta · Mar 2012
Enhanced charge-independent mitochondrial free Ca(2+) and attenuated ADP-induced NADH oxidation by isoflurane: Implications for cardioprotection.
Modulation of mitochondrial free Ca(2+) ([Ca(2+)](m)) is implicated as one of the possible upstream factors that initiates anesthetic-mediated cardioprotection against ischemia-reperfusion (IR) injury. To unravel possible mechanisms by which volatile anesthetics modulate [Ca(2+)](m) and mitochondrial bioenergetics, with implications for cardioprotection, experiments were conducted to spectrofluorometrically measure concentration-dependent effects of isoflurane (0.5, 1, 1.5, 2mM) on the magnitudes and time-courses of [Ca(2+)](m) and mitochondrial redox state (NADH), membrane potential (ΔΨ(m)), respiration, and matrix volume. ⋯ These findings suggest that isoflurane's effects are mediated in part at the mitochondrial level: (1) to enhance the net rate of state 2 Ca(2+) uptake by inhibiting the Na(+)/Ca(2+) exchanger (NCE), independent of changes in ΔΨ(m) and matrix volume, and (2) to decrease the rates of state 3 electron transfer and ADP phosphorylation by inhibiting complex I. These direct effects of isoflurane to increase [Ca(2+)](m), while depressing NCE activity and oxidative phosphorylation, could underlie the mechanisms by which isoflurane provides cardioprotection against IR injury at the mitochondrial level.
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Physical activity has been recognized as an important protective factor reducing disability and mortality and therefore it is focus of many health promotion activities at all ages. More recently a growing body of literature is focusing whether physical activity could also have a positive impact on brain aging with exploring healthy brain aging as well as on cognitive impairment and dementia. An increasing number of prospective studies and randomized controlled trials involving humans take place both with older adults with normal cognition as well as with mild cognitive impairment or dementia. ⋯ Increasingly research into underlying mechanisms in relation to physical activity and brain aging identify biomarker candidates with especially neuroimaging measurements being more used in trials with humans. Whilst the evidence base is slowly growing more detailed research is needed to address methodological issues to finally achieve clinical relevance. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.
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Although in the last decade brain activation in healthy aging and dementia was mainly studied using task-activation fMRI, there is increasing interest in task-induced decreases in brain activity, termed deactivations. These deactivations occur in the so-called default mode network (DMN). In parallel a growing number of studies focused on spontaneous, ongoing 'baseline' activity in the DMN. ⋯ Even subjects at risk for developing AD, either in terms of having amyloid plaques or carrying the APOE4 allele, showed disruptions in the DMN. While fMRI is a useful tool for detecting changes in DMN functional connectivity and deactivation, more work needs to be conducted to conclude whether these measures will become useful as a clinical diagnostic tool in AD. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.