ABSTRACT
Several lines of evidence show that decreased metabolic rate precedes cognitive impairment in Alzheimer s disease (AD). Decreased neuronal metabolism contributes to neuronal atrophy and functional impairment and is thus an early occurring hallmark of AD. Factors that may contribute to a diminishment in neuronal metabolism are age, sex, APOE-ε 4 and decreased levels of sex hormones or melatonin. Several observations in postmortem brain indicate that activated neurons are better able to withstand aging and AD, a phenomenon we paraphrased as use it or lose it. Moreover, a number of pharmacological and non-pharmacological studies support the concept that activation of the brain has beneficial effects and may to a certain degree restore several aspects of cognition and other central functions. For instance, the circadian system of Alzheimer patients may be restimulated by exposing them to more light or transcutaneous nerve stimulation. A procedure allowing testing of the efficacy of putative stimulatory compounds such as neurotrophins and precursor cells has been developed in order to be able to culture human postmortem brain tissue.
Subject(s)
Alzheimer Disease , Apoenzymes , Atrophy , Basal Nucleus of Meynert , Nerve Degeneration , Neurology , Neurons , Receptor, trkA , Suprachiasmatic NucleusABSTRACT
Objective To investigate whether N-methyl-D-aspartate(NMDA) signal pathway is involved in platelet-activating factor(PAF)-induced apoptosis in neurons.Methods Mice cortex neurons were treated by PAF in different dose for 24 hours or pretreated by a PAF receptor antagonist BN52021, an NMDA receptor antagonist MK801 and a nitric oxide synthase(NOS) inhibitor L-NAME for 30 min. Then the neurons were stained by propidium iodide(PI)/calcein AM and the images were taken by a digital camera on a fluorescent microscope. Neuron death ratio(%) was calculated. In the mean time, neuron NOS(nNOS) expression of the cells was detected by Western Blot method, as well as nNOS activity was measured by 3H radioimmunoassay.Results (1)Neuronal death increased after neurons were treated with 0.01, 0.1, 0.3 and 0.6 ?mol/L PAF 24 h. There were signifitantly changed in 0.3 ?mol/L and 0.6?mol/L comparing control. (2)PAF-induced neurotoxicity was prevented not only by BN5021, but also by MK-801 or L-NAME. (3)PAF enhanced nNOS expression and activity in neurons.Conclusion NMDA signal pathway is involved in platelet-activating factor-induced neurotoxicity.
ABSTRACT
Objective: To investigate the regulation of PTEN on apoptosis and the active roles in blocking Ca2+ influx and neuroprotection.Methods: In the OGD model with anaerobic gas mixture and deoxygenated,glucose-free extracellular solution,shRNAspten-GFP and unrelated control plasmid PshGFP transfection were done respectively.Intracellular free calcium concentration were measured with Fura-2 AM fluorescent indicator,the expression of PTEN were analyzed by immunoblotting(blot) and neuron apoptosis were detected by AO/EB and Flow Cytometry.Results: Apoptosis rate and calcium concentration after OGD was significantly higher than that of normal group(P
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Objective To confirm that if the integrality of NF has effect on the shape and distribution of NLY. Methods using SABC monocolon antibody immunohistochemistry,electron microscopy,immunocytochemistry, and enzymocytochemistry to observe the disorder of NF-H and the changes of distribution and shape of NLY after vanadate treated. Results When the integrality of NF was damaged, the proteins of NF gathered towards nuclear accompany with the similar movements of NLY, meanwhile the shape of NLY also changed into round from thread-like shape.Conclusion Through different ways we used, vanadate can over-phosphate NF proteins and destroy the assemble ability. Whether NF has a complete structure is important to the shape and distribution of NLY, which will be changed when the structure of NF is disorganized.