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Articles, Neurobiology of Disease

A Reporter of Local Dendritic Translocation Shows Plaque- Related Loss of Neural System Function in APP-Transgenic Mice

Melanie Meyer-Luehmann, Matthew Mielke, Tara L. Spires-Jones, Will Stoothoff, Phill Jones, Brian J. Bacskai and Bradley T. Hyman
Journal of Neuroscience 7 October 2009, 29 (40) 12636-12640; DOI: https://doi.org/10.1523/JNEUROSCI.1948-09.2009
Melanie Meyer-Luehmann
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Matthew Mielke
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Tara L. Spires-Jones
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Will Stoothoff
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Phill Jones
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Brian J. Bacskai
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Bradley T. Hyman
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    Figure 1.

    BDNF stimulates protein synthesis of the GFP and Venus reporter in primary neurons. a–c, A neuron transfected with 3′-UTR CAMKIIαEGFP 5′-UTR reporter and treated for 75 min with BDNF. Before BDNF application, the GFP signal is very modest (a). After 45 and 75 min, the fluorescent signal increases dramatically in the cell body (arrow) as well as in the neurites (arrowhead) (b, c). d, g, An untreated and BDNF-treated cultured neuron expressing the Venus reporter. The BDNF-treated cell shows enhanced fluorescence after 75 min in the cell body (arrow) and neurites (arrowhead) (h) in contrast to the untreated control cell (e). f, i, Summary data for all untreated and BDNF-treated cell bodies and neurites. The intensity remains unchanged in the control neurons and only changes in the stimulated neurons. Note that the intensity is significantly higher after only 30 min of BDNF stimulation in both the cell body (f) and neurites (i) and increases over time (*p < 0.0001). j, A schematic representation of the constructs used for this experiment. Scale bars: a–c, 15 μm; d, e, g, h, 15 μm.

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    Figure 2.

    Fluorescence intensity measured postmortem is decreased in neurons surrounding plaques and remains unaltered after environmental stimulation. a–f, Representative neurons from wild-type (WT) and transgenic (TG) mice that differ in their fluorescence intensity. Fluorescence intensity from transgenic neurons in the vicinity of plaques (shown in blue; a) was greatly overall reduced compared with wild-type neurons and remained unchanged after environmental stimulation (b, e). Interestingly, fluorescence intensity from neurons >100 μm away from plaques (c) was significantly higher than those from close to plaques and increased in the cell body (arrow) after environmental stimulation (d). Note that the intensity in the wild-type neurons started at an even higher level (e) and increased further after enriched environment (f) in the cell body (arrow) as well as in neurites (arrowhead). g–i, Intensity measurements confirmed that transgenic neurons had significantly decreased intensity (*p < 0.0001), and only wild-type neurons increased intensity in both cell bodies (*p < 0.0001) (g) as well as in neurites (*p < 0.0001) (h) after environmental enrichment. Scale bar: a–f, 20 μm.

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    Figure 3.

    Individual dendritic segments in close proximity to a plaque have decreased neuronal activity. a, b, A neuron and a schematic illustration of a neuron filled with Venus in the vicinity of a plaque (shown in blue). White and black boxes mark the segments where intensity was measured. Note the decreased intensity in the segment close to the plaque indicated by the arrow. c, Dendritic segments farther from the plaque had a statistically significant higher intensity when compared with the dendritic segments nearest to the plaque in unstimulated as well as in stimulated neurons (*p < 0.0001). Scale bar: a, 10 μm.

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The Journal of Neuroscience: 29 (40)
Journal of Neuroscience
Vol. 29, Issue 40
7 Oct 2009
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A Reporter of Local Dendritic Translocation Shows Plaque- Related Loss of Neural System Function in APP-Transgenic Mice
Melanie Meyer-Luehmann, Matthew Mielke, Tara L. Spires-Jones, Will Stoothoff, Phill Jones, Brian J. Bacskai, Bradley T. Hyman
Journal of Neuroscience 7 October 2009, 29 (40) 12636-12640; DOI: 10.1523/JNEUROSCI.1948-09.2009

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A Reporter of Local Dendritic Translocation Shows Plaque- Related Loss of Neural System Function in APP-Transgenic Mice
Melanie Meyer-Luehmann, Matthew Mielke, Tara L. Spires-Jones, Will Stoothoff, Phill Jones, Brian J. Bacskai, Bradley T. Hyman
Journal of Neuroscience 7 October 2009, 29 (40) 12636-12640; DOI: 10.1523/JNEUROSCI.1948-09.2009
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