Department of Neurology, NorthShore University HealthSystem, Glenview, IL.Disease-a-month: DM (Impact Factor: 0.95). 12/2012; 58(12):666-677. DOI: 10.1016/j.disamonth.2012.08.008
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- "No accepted biomarker for Alzheimer's disease exists, and this disease can only by diagnosed by brain biopsy or autopsy clinics. The key issue in the current study was to improve the accuracy of clinical diagnosis of Alzheimer's disease and to improve the sensitivity of early diagnosis of this disease. "
ABSTRACT: 3.0T magnetic resonance spectroscopic imaging is a commonly used method in the research of brain function in Alzheimer's disease. However, the role of 7.0T high-field magnetic resonance spectroscopic imaging in brain function of Alzheimer's disease remains unclear. In this study, 7.0T magnetic resonance spectroscopy showed that in the hippocampus of Alzheimer's disease rats, the N-acetylaspartate wave crest was reduced, and the creatine and choline wave crest was elevated. This finding was further supported by hematoxylin-eosin staining, which showed a loss of hippocampal neurons and more glial cells. Moreover, electron microscopy showed neuronal shrinkage and mitochondrial rupture, and scanning electron microscopy revealed small size hippocampal synaptic vesicles, incomplete synaptic structure, and reduced number. Overall, the results revealed that 7.0T high-field nuclear magnetic resonance spectroscopy detected the lesions and functional changes in hippocampal neurons of Alzheimer's disease rats in vivo, allowing the possibility for assessing the success rate and grading of the amyloid beta (1-40) animal model of Alzheimer's disease.Neural Regeneration Research 02/2014; 9(4):430-5. DOI:10.4103/1673-5374.128255 · 0.22 Impact Factor
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ABSTRACT: Recent studies suggest that the toxic effects of Aβ can be attributed to its capability to insert in membranes and form pore-like structures, which are permeable to cations and molecules such as ATP. Our working hypothesis is that Aβ increases extracellular ATP causing activation of P2X receptors and potentiating excitatory synaptic activity. We found that soluble oligomers of β-amyloid peptide increased cytosolic Ca2+ 4-fold above control (415±28% of control). Also, ATP leakage (157±10% of control) was independent of extracellular Ca2+, suggesting that ATP traveled from the cytosol through an Aβ pore-mediated efflux and not from exocytotic mechanisms. The subsequent activation of P2XR by ATP can contribute to the cytosolic Ca2+ increase observed with Aβ. Additionally, we found that β-amyloid oligomers bind preferentially to excitatory neurons inducing an increase in excitatory synaptic current frequency (248.1±32.7%) that was blocked by the use of P2XR antagonists such as PPADS (Aβ+PPADS: 110.9±18.35%) or Apyrase plus DPCPX (Aβ+inhibitors: 98.97±17.4%). Taken together, we suggest that Aβ induces excitotoxicity by binding preferentially to excitatory neuron membranes forming a non-selective pore and by increasing intracellular calcium by itself and through P2XR activation by extracellular ATP leading to an augmention in mEPSC activity. All these effects were blocked with a non-specific P2XR antagonist, indicating that part of the neurotoxicity of Aβ is mediated by P2XR activation and facilitation of excitatory neurotransmitter release. These findings suggest that P2XR can be considered as a potential new target for the development of drugs or pharmacological tools to treat Alzheimer's disease. Copyright © 2015. Published by Elsevier Ltd.Neuropharmacology 04/2015; 100. DOI:10.1016/j.neuropharm.2015.04.005 · 5.11 Impact Factor
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