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Vasoactive Intestinal Peptide Decreases β-Amyloid Accumulation and Prevents Brain Atrophy in the 5xFAD Mouse Model of Alzheimer’s Disease

  • Orhan Tansel Korkmaz
  • Hakan Ay
  • Nurgul Aytan
  • Isabel Carreras
  • Neil W. Kowall
  • Alpaslan Dedeoglu
  • Nese Tuncel
Article

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by extracellular deposits of fibrillary β-amyloid (Aβ) plaques in the brain that initiate an inflammatory process resulting in neurodegeneration. The neuronal loss associated with AD results in gross atrophy of affected regions causing a progressive loss of cognitive ability and memory function, ultimately leading to dementia. Growing evidence suggests that vasoactive intestinal peptide (VIP) could be beneficial for various neurodegenerative diseases, including AD. The study investigated the effects of VIP on 5xFAD, a transgenic mouse model of AD. Toward this aim, we used 20 5xFAD mice in two groups (n = 10 each), VIP-treated (25 ng/kg i.p. injection, three times per week) and saline-treated (the drug’s vehicle) following the same administration regimen. Treatment started at 1 month of age and ended 2 months later. After 2 months of treatment, the mice were euthanized, their brains dissected out, and immunohistochemically stained for Aβ40 and Aβ42 on serial sections. Then, plaque analysis and stereological morphometric analysis were performed in different brain regions. Chronic VIP administration in 5xFAD mice significantly decreased the levels of Aβ40 and Aβ42 plaques in the subiculum compared to the saline treated 5xFAD mice. VIP treatment also significantly decreased Aβ40 and Aβ42 plaques in cortical areas and significantly increased the hippocampus/cerebrum and corpus callosum/cerebrum ratio but not the cerebral cortex/cerebrum ratio. In summary, we found that chronic administration of VIP significantly decreased Aβ plaques and preserved against atrophy for related brain regions in 5xFAD AD mice.

Keywords

Alzheimer’s disease Vasoactive intestinal peptide β-Amyloid plaques Brain atrophy Neuroinflammation 5xFAD 

Notes

Acknowledgements

The authors thank to Lokman Hossain for animal husbandry.

Funding

This research is supported by grants from NIA (R01AG031896, RF1AG056032) and the Department of Veteran Affairs (Merit Award; 5I01BX001875-03) to A. Dedeoglu and P30AG013846 to NW Kowall, and Scientific and Technical Research Council of Turkey (TUBITAK, 1059B190900502) to O.T. Korkmaz.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Research and DevelopmentVA Boston Healthcare SystemBostonUSA
  2. 2.Department of NeurologyBoston University School of MedicineBostonUSA
  3. 3.Department of Physiology, Faculty of MedicineEskisehir Osmangazi UniversityEskisehirTurkey
  4. 4.Faculty of Medicine, Department of PhysiologyEskisehir Osmangazi UniversityEskisehirTurkey
  5. 5.Department of Anatomy, Faculty of MedicineEskisehir Osmangazi UniversityEskisehirTurkey
  6. 6.Department of BiochemistryBoston University School of MedicineBostonUSA
  7. 7.Department of RadiologyMGH and Harvard Medical SchoolBostonUSA

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