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Early Changes in Hyppocampal Neurogenesis Induced by Soluble Aβ1-42 Oligomers

  • Yu. K. Komleva
  • O. L. Lopatina
  • Ya. V. Gorina
  • A. I. Chernykh
  • A. N. Shuvaev
  • A. B. Salmina
Article
  • 13 Downloads

Abstract

Alzheimer’s disease (AD) is characterized by the loss of neurons, the accumulation of intracellular neurofibrillary tangles and extracellular amyloid plaques in the brain. However, contradicting data exist on differences in neurogenesis at the onset of the disease or before the formation of amyloid plaques. Taking into consideration growing awareness of the importance of the pre-symptomatic phase in neurodegenerative diseases in the context of early diagnosis and pathogenesis, we have analyzed critical periods of adult hippocampal neurogenesis at the early stage under the action of soluble forms of amyloid-beta (Aβ1-42). Using the mouse AD model induced by injection of soluble Aβ oligomers we investigated proliferation, migration, and neuronal cells survival. The injection of Aβ1-42 oligomers caused a decrease in cell proliferation in the mouse hippocampus. Despite preservation of the neuroblast pool in animals treated with Aβ injection, the process of radial migration impaired, and apoptosis increased. Thus, our results demonstrate that Aβ administration impaired critical stages of neurogenesis including progenitor cells, neuroblast migration, integration of immature neurons, and survival of neurons under application of soluble beta-amyloid oligomers. The data obtained indicate the decline in proliferation rate in the subgranular zone, which is accompanied by ectopic differentiation and disturbed migration, producing, apparently, abnormal neurons that have lower survival rates. That could lead to a decrease in the number of mature neurons and in the number of cells in the granular layer of the dentate gyrus.

Keywords:

Alzheimer’s disease neurogenesis subgranular zone cell migration apoptosis stem cells 

Notes

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Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • Yu. K. Komleva
    • 1
    • 2
  • O. L. Lopatina
    • 1
    • 2
  • Ya. V. Gorina
    • 1
    • 2
  • A. I. Chernykh
    • 2
  • A. N. Shuvaev
    • 2
  • A. B. Salmina
    • 1
    • 2
  1. 1.Department of Biochemistry, Medical, Pharmaceutical, and Toxicological Chemistry, Prof. Voino-Yasenetsky Krasnoyarsk State Medical UniversityKrasnoyarskRussia
  2. 2.Research Institute of Molecular Medicine and Pathobiochemistry, Prof. Voino-Yasenetsky Krasnoyarsk State Medical UniversityKrasnoyarskRussia

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