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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: There are conflicting data regarding alterations in β-amyloid precursor protein (APP) mRNAs in Alzheimer's disease (AD). This may be due partly to variables such as agonal state and choice of control group. We have used in situ hybridization histochemistry to study expression of APP mRNAs, with and without the domain encoding the Kunitz protease inhibitor, in a way that overcomes some of the limitations of the current data. Tissue from frontal cortex was collected at rapid autopsy from patients with AD or other cognitive impairments whose terminal phase was prospectively assessed. There were three main findings. Firstly, the amount of APP mRNAs correlated strongly with glutamate decarboxylase activity and was reduced in association with terminal pyrexia. These correlations suggest that agonal state affects APP mRNA and, therefore, that differences in premortem course may contribute to the varying changes in APP transcript abundance reported in AD. Secondly, a reduction of both forms of APP mRNA, normalized to polyadenylated mRNA, was found in AD compared with normal controls and with non-AD dementias. This supports findings that the APP-related pathology of AD is not due to overexpression of APP mRNA or an altered proportion of Kunitz protease inhibitor-containing isoforms. Thirdly, the amount of APP mRNA correlated inversely with that of heat-shock protein (hsx70) mRNA. This relationship was unexpected given current theories that APP expression occurs as part of a stress response, and suggests that other factors predominate in determining neocortical APP mRNA content in neurodegenerative disorders.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 22 (2005), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Calcineurin (protein phosphatase 2B) is a calcium-dependent serine-threonine phosphatase. It has diverse roles and is centrally involved in synaptic plasticity. The catalytic A subunit of calcineurin has three isoforms, α, β and γ. Their expression and ontogeny in the brain has not been systematically investigated; such data become important with a report that PPP3CC, the gene encoding calcineurin Aγ, is a susceptibility gene for schizophrenia, and the finding that its expression is decreased in the disorder. We used in situ hybridization histochemistry to measure the relative transcript abundance of calcineurin Aγ and the other catalytic isoforms, Aα and Aβ, during development of the Sprague–Dawley rat hippocampus and cerebellum. All three isoforms are present in both regions at all time points [embryonic day 19 (E19) to postnatal day 42 (P42)] and undergo developmental regulation, but differ in their ontogenic profile. Calcineurin Aα and Aβ mRNAs increased from E19 through to adulthood, whereas Aγ mRNA was most highly expressed during early developmental stages. Calcineurin Aα and Aβ mRNAs positively correlated with synaptophysin mRNA (a synaptic marker), whilst Aγ mRNA was either unrelated to, or negatively correlated, with this transcript. These data confirm that all three calcineurin A subunits are expressed in the rodent brain, and indicate that calcineurin Aγ may have different roles than Aα and Aβ. The data also suggest a potential importance of calcineurin Aγ in neurodevelopment, and in the genetically influenced neurodevelopmental disturbance that is thought to underlie schizophrenia.
    Type of Medium: Electronic Resource
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