103 research outputs found

    Short-Term Environmental Enrichment Rescues Adult Neurogenesis and Memory Deficits in APPSw,Ind Transgenic Mice

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    Epidemiological studies indicate that intellectual activity prevents or delays the onset of Alzheimer's disease (AD). Similarly, cognitive stimulation using environmental enrichment (EE), which increases adult neurogenesis and functional integration of newborn neurons into neural circuits of the hippocampus, protects against memory decline in transgenic mouse models of AD, but the mechanisms involved are poorly understood. To study the therapeutic benefits of cognitive stimulation in AD we examined the effects of EE in hippocampal neurogenesis and memory in a transgenic mouse model of AD expressing the human mutant β-amyloid (Aβ) precursor protein (APPSw,Ind). By using molecular markers of new generated neurons (bromodeoxiuridine, NeuN and doublecortin), we found reduced neurogenesis and decreased dendritic length and projections of doublecortin-expressing cells of the dentate gyrus in young APPSw,Ind transgenic mice. Moreover, we detected a lower number of mature neurons (NeuN positive) in the granular cell layer and a reduced volume of the dentate gyrus that could be due to a sustained decrease in the incorporation of new generated neurons. We found that short-term EE for 7 weeks efficiently ameliorates early hippocampal-dependent spatial learning and memory deficits in APPSw,Ind transgenic mice. The cognitive benefits of enrichment in APPSw,Ind transgenic mice were associated with increased number, dendritic length and projections to the CA3 region of the most mature adult newborn neurons. By contrast, Aβ levels and the total number of neurons in the dentate gyrus were unchanged by EE in APPSw,Ind mice. These results suggest that promoting the survival and maturation of adult generated newborn neurons in the hippocampus may contribute to cognitive benefits in AD mouse models

    Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics

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    Antibodies to Alzheimer Neurofibrillary Tangles

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    Antibodies to Alzheimer Neurofibrillary Tangles

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    Isolation and chromosomal mapping of human glycogen synthase kinase-3α and -3β encoding genes

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    Glycogen synthase kinase-3 (GSK-3) is a serine-threonine kinase that exists as two isoforms, α and β, encoded by separate genes. Phosphorylation targets include a variety of cytoplasmic and nuclear proteins. Recent studies found that neurofilaments, amyloid precursor protein, and tau proteins are substrates of GSK-3 and that aberrant phosphorylation of these proteins is implicated in pathologies of the nervous system. To analyse the organisation of these two genes, a YAC library was screened by polymerase chain reaction, using primers specific for human GSK-3α and GSK-3β cDNA. TWo clones, 220 and 285 kb m size, containing the complete GSK-3α coding sequence, and two clones, 365 and 285 kb in size, containing the 5' coding sequence of GSK-3β, were isolated. By somatic cell hybrid panel DNA amplification and radiation hybrid mapping, GSK-3α was found to be located at 19q13.2. On the other hand, by somatic cell hybrid panel DNA amplification and fluorescence in situ hybridisation using the 285-kb YAC clone, GSK-3β was mapped to 3q13.3.link_to_subscribed_fulltex
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