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Brief Communications

Ligand for Translocator Protein Reverses Pathology in a Mouse Model of Alzheimer's Disease

Anna M. Barron, Luis M. Garcia-Segura, Donatella Caruso, Anusha Jayaraman, Joo-Won Lee, Roberto C. Melcangi and Christian J. Pike
Journal of Neuroscience 15 May 2013, 33 (20) 8891-8897; DOI: https://doi.org/10.1523/JNEUROSCI.1350-13.2013
Anna M. Barron
1Davis School of Gerontology, University of Southern California, Los Angeles, California 90089,
2Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan,
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Luis M. Garcia-Segura
3Instituto Cajal, CSIC, E-28002 Madrid, Spain, and
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Donatella Caruso
4Department of Pharmacological and Biomolecular Sciences, Center of Excellence on Neurodegenerative Diseases, University of Milan, 20133 Milan, Italy
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Anusha Jayaraman
1Davis School of Gerontology, University of Southern California, Los Angeles, California 90089,
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Joo-Won Lee
1Davis School of Gerontology, University of Southern California, Los Angeles, California 90089,
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Roberto C. Melcangi
4Department of Pharmacological and Biomolecular Sciences, Center of Excellence on Neurodegenerative Diseases, University of Milan, 20133 Milan, Italy
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Christian J. Pike
1Davis School of Gerontology, University of Southern California, Los Angeles, California 90089,
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    Figure 1.

    Ro5-4864 reduces Aβ accumulation in the hippocampus of 3xTgAD mice. A–J, Representative photomicrographs show Aβ immunoreactivity in hippocampus CA1 (A–E) and subiculum (F–J) regions of 7-month-old 3xTgAD mice in the sham + vehicle (A, F), GDX + vehicle (B, G), and GDX + Ro5-4864 (C, H) conditions; and 24-month-old 3xTgAD mice administered vehicle (D, I) and Ro5-4864 (E, J). Data show mean Aβ immunoreactivity loads (±SEM) in 3xTgAD mice at ages 7 months (solid bars, left axis) and 24 months (open bars, right axis) in hippocampus CA1 (K) and subiculum (L). *p < 0.05, compared with all other groups.

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    Figure 2.

    Ro5-4864 reduces hippocampal gliosis in 3xTgAD mice. A–J, Representative photomicrographs show GFAP (A–E) and IBA-1 (F–J) immunoreactivities in the hippocampus CA1 region of 7-month-old 3xTgAD mice in the sham + vehicle (A, F), GDX + vehicle (B, G), and GDX + Ro5-4864 (C, H) conditions; and 24-month-old 3xTgAD mice administered vehicle (D, I) and Ro5-4864 (E, J). K, GFAP immunoreactivity volume density values (±SEM) in the hippocampus CA1 region. L, IBA-1 immunoreactivity volume density values (±SEM) in the hippocampus CA1 region. #p < 0.001, compared with GDX + vehicle. *p < 0.001, compared with all other groups.

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    Figure 3.

    Ro5-4864 regulates brain testosterone and progesterone levels and improves behavioral deficits in 3xTgAD mice. A, Brain testosterone levels were quantified in limbic structures. Ro5-4864 treatment attenuated GDX-induced testosterone depletion in young-adult 7-month-old mice. B, Brain progesterone levels were quantified in limbic structures. Ro5-4864 treatment increased PROG more than twofold in GDX 7-month-old mice. C, Percentage duration (±SEM) spent exploring the open arm of the EPM, with increased exploration of the open arm indicative of reduced anxiety. D, SAB, represented as percentage alternation (±SEM); both 7-month-old GDX and 24-month-old 3xTgAD mice administered Ro5-4864 exhibited significantly improved SAB performance. #p < 0.05, compared with sham + vehicle. *p < 0.05, compared with all other groups.

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    Figure 4.

    Ro5-4864 alone or in combination with PK-11195 reduces brain Aβ levels in non-Tg mice. Brain levels of soluble AβX-40 (A) and AβX-42 (B) from hemibrain homogenates were assessed by ELISA in young-adult non-Tg mice treated for 4 weeks with vehicle, Ro5-4864, PK11195, or Ro5-4864 + PK11195. Data are mean ± SEM. *p < 0.02, compared with GDX + vehicle. ‡p < 0.001, compared with GDX + vehicle.

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The Journal of Neuroscience: 33 (20)
Journal of Neuroscience
Vol. 33, Issue 20
15 May 2013
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Ligand for Translocator Protein Reverses Pathology in a Mouse Model of Alzheimer's Disease
Anna M. Barron, Luis M. Garcia-Segura, Donatella Caruso, Anusha Jayaraman, Joo-Won Lee, Roberto C. Melcangi, Christian J. Pike
Journal of Neuroscience 15 May 2013, 33 (20) 8891-8897; DOI: 10.1523/JNEUROSCI.1350-13.2013

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Ligand for Translocator Protein Reverses Pathology in a Mouse Model of Alzheimer's Disease
Anna M. Barron, Luis M. Garcia-Segura, Donatella Caruso, Anusha Jayaraman, Joo-Won Lee, Roberto C. Melcangi, Christian J. Pike
Journal of Neuroscience 15 May 2013, 33 (20) 8891-8897; DOI: 10.1523/JNEUROSCI.1350-13.2013
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