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The effect of focal brain injury on beta-amyloid plaque deposition, inflammation and synapses in the APP/PS1 mouse model of Alzheimer's disease.

Abstract

Traumatic brain injury is a risk factor for Alzheimer's disease (AD), however the effect of such neural damage on the onset and progression of beta-amyloid (Aβ) plaque pathology is not well understood. This study utilized an in vivo model of focal brain injury to examine how localized damage may acutely affect the onset and progression of Aβ plaque deposition as well as inflammatory and synaptic changes, in the APP/PS1 (APPSWE, PSEN1dE9) transgenic model of AD relative to wild-type (Wt) mice. Acute focal brain injury in 3- and 9-month-old APP/PS1 and Wt mice was induced by insertion of a needle into the somatosensory neocortex, as compared to sham surgery, and examined at 24h and 7d post-injury (PI). Focal brain injury did not induce thioflavine-S stained or (pan-Aβ antibody) MOAB-2-labeled plaques at either 24h or 7d PI in 3-month-old APP/PS1 mice or Wt mice. Nine-month-old APP/PS1 mice demonstrate cortical Aβ plaques but focal injury had no statistically significant (p>0.05) effect on thioflavine-S or MOAB-2 plaque load surrounding the injury site at 24h PI or 7d PI. There was a significant (p<0.001) increase in cross-sectional cortical area occupied by Iba-1 positive microglia in injured mice compared to sham animals, however this response did not differ between APP/PS1 and Wt mice (p>0.05). For both Wt and APP/PS1 mice alike, synaptophysin puncta near the injury site were significantly reduced 24h PI (compared to sites distant to the injury and the corresponding area in sham mice; p<0.01), but not after 7d PI (p>0.05). There was no significant effect of genotype on this response (p>0.05). These results indicate that focal brain injury and the associated microglial response do not acutely alter Aβ plaque deposition in the APP/PS1 mouse model. Furthermore the current study demonstrated that the brains of both Wt and APP/PS1 mice are capable of recovering lost synaptophysin immunoreactivity post-injury, the latter in the presence of Aβ plaque pathology that causes synaptic degeneration.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Wicking Dementia Research and Education Centre, University of Tasmania, Australia. Electronic address: Jessica.Collins@utas.edu.au.

    ,

    Wicking Dementia Research and Education Centre, University of Tasmania, Australia.

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    Wicking Dementia Research and Education Centre, University of Tasmania, Australia.

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    Wicking Dementia Research and Education Centre, University of Tasmania, Australia; School of Medicine, University of Tasmania, Australia.

    Wicking Dementia Research and Education Centre, University of Tasmania, Australia; School of Medicine, University of Tasmania, Australia.

    Source

    Experimental neurology 267: 2015 May pg 219-29

    MeSH

    Age Factors
    Alzheimer Disease
    Amyloid beta-Peptides
    Amyloid beta-Protein Precursor
    Animals
    Brain Injuries
    Calcium-Binding Proteins
    Disease Models, Animal
    Encephalitis
    Gene Expression Regulation
    Humans
    Macrophages
    Mice
    Mice, Inbred C57BL
    Mice, Transgenic
    Microfilament Proteins
    Microglia
    Nerve Tissue Proteins
    Plaque, Amyloid
    Presenilin-1
    Synapses
    Time Factors

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    25747037

    Citation

    Collins, Jessica M., et al. "The Effect of Focal Brain Injury On Beta-amyloid Plaque Deposition, Inflammation and Synapses in the APP/PS1 Mouse Model of Alzheimer's Disease." Experimental Neurology, vol. 267, 2015, pp. 219-29.
    Collins JM, King AE, Woodhouse A, et al. The effect of focal brain injury on beta-amyloid plaque deposition, inflammation and synapses in the APP/PS1 mouse model of Alzheimer's disease. Exp Neurol. 2015;267:219-29.
    Collins, J. M., King, A. E., Woodhouse, A., Kirkcaldie, M. T., & Vickers, J. C. (2015). The effect of focal brain injury on beta-amyloid plaque deposition, inflammation and synapses in the APP/PS1 mouse model of Alzheimer's disease. Experimental Neurology, 267, pp. 219-29. doi:10.1016/j.expneurol.2015.02.034.
    Collins JM, et al. The Effect of Focal Brain Injury On Beta-amyloid Plaque Deposition, Inflammation and Synapses in the APP/PS1 Mouse Model of Alzheimer's Disease. Exp Neurol. 2015;267:219-29. PubMed PMID: 25747037.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The effect of focal brain injury on beta-amyloid plaque deposition, inflammation and synapses in the APP/PS1 mouse model of Alzheimer's disease. AU - Collins,Jessica M, AU - King,Anna E, AU - Woodhouse,Adele, AU - Kirkcaldie,Matthew T K, AU - Vickers,James C, Y1 - 2015/03/04/ PY - 2014/09/16/received PY - 2015/01/11/revised PY - 2015/02/27/accepted PY - 2015/3/10/entrez PY - 2015/3/10/pubmed PY - 2015/7/7/medline KW - APP/PS1 KW - Alzheimer's disease KW - Beta-amyloid KW - Brain injury KW - Microglia KW - Synapses SP - 219 EP - 29 JF - Experimental neurology JO - Exp. Neurol. VL - 267 N2 - Traumatic brain injury is a risk factor for Alzheimer's disease (AD), however the effect of such neural damage on the onset and progression of beta-amyloid (Aβ) plaque pathology is not well understood. This study utilized an in vivo model of focal brain injury to examine how localized damage may acutely affect the onset and progression of Aβ plaque deposition as well as inflammatory and synaptic changes, in the APP/PS1 (APPSWE, PSEN1dE9) transgenic model of AD relative to wild-type (Wt) mice. Acute focal brain injury in 3- and 9-month-old APP/PS1 and Wt mice was induced by insertion of a needle into the somatosensory neocortex, as compared to sham surgery, and examined at 24h and 7d post-injury (PI). Focal brain injury did not induce thioflavine-S stained or (pan-Aβ antibody) MOAB-2-labeled plaques at either 24h or 7d PI in 3-month-old APP/PS1 mice or Wt mice. Nine-month-old APP/PS1 mice demonstrate cortical Aβ plaques but focal injury had no statistically significant (p>0.05) effect on thioflavine-S or MOAB-2 plaque load surrounding the injury site at 24h PI or 7d PI. There was a significant (p<0.001) increase in cross-sectional cortical area occupied by Iba-1 positive microglia in injured mice compared to sham animals, however this response did not differ between APP/PS1 and Wt mice (p>0.05). For both Wt and APP/PS1 mice alike, synaptophysin puncta near the injury site were significantly reduced 24h PI (compared to sites distant to the injury and the corresponding area in sham mice; p<0.01), but not after 7d PI (p>0.05). There was no significant effect of genotype on this response (p>0.05). These results indicate that focal brain injury and the associated microglial response do not acutely alter Aβ plaque deposition in the APP/PS1 mouse model. Furthermore the current study demonstrated that the brains of both Wt and APP/PS1 mice are capable of recovering lost synaptophysin immunoreactivity post-injury, the latter in the presence of Aβ plaque pathology that causes synaptic degeneration. SN - 1090-2430 UR - https://www.unboundmedicine.com/medline/citation/25747037/The_effect_of_focal_brain_injury_on_beta_amyloid_plaque_deposition_inflammation_and_synapses_in_the_APP/PS1_mouse_model_of_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(15)00064-3 DB - PRIME DP - Unbound Medicine ER -