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Adult Neural Stem Cell Migration Is Impaired in a Mouse Model of Alzheimer's Disease

Fecha de publicación: Fecha Ahead of Print:

Autores de CIPF

Participantes ajenos a CIPF

  • Esteve, D
  • Molina-Navarro, MM
  • Martinez-Varea, N
  • Blanco-Gandia, MC
  • Rodriguez-Arias, M
  • Vina, J
  • Lloret, A

Abstract

Neurogenesis in the adult brain takes place in two neurogenic niches: the ventricular-subventricular zone (V-SVZ) and the subgranular zone. After differentiation, neural precursor cells (neuroblasts) have to move to an adequate position, a process known as neuronal migration. Some studies show that in Alzheimer's disease, the adult neurogenesis is impaired. Our main aim was to investigate some proteins involved both in the physiopathology of Alzheimer's disease and in the neuronal migration process using the APP/PS1 Alzheimer's mouse model. Progenitor migrating cells are accumulated in the V-SVZ of the APP/PS1 mice. Furthermore, we find an increase of Cdh1 levels and a decrease of Cdk5/p35 and cyclin B1, indicating that these cells have an alteration of the cell cycle, which triggers a senescence state. We find less cells in the rostral migratory stream and less mature neurons in the olfactory bulbs from APP/PS1 mice, leading to an impaired odour discriminatory ability compared with WT mice. Alzheimer's disease mice present a deficit in cell migration from V-SVZ due to a senescent phenotype. Therefore, these results can contribute to a new approach of Alzheimer's based on senolytic compounds or pro-neurogenic factors.

Datos de la publicación

ISSN/ISSNe:
0893-7648, 1559-1182

MOLECULAR NEUROBIOLOGY  SPRINGER

Tipo:
Article
Páginas:
1168-1182
PubMed:
34894324

Citas Recibidas en Web of Science: 17

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Keywords

  • Subventricular zone; Beta-amyloid toxicity; Neurogenesis; Senescence; Olfaction

Campos de Estudio

Financiación

Conselleria, de Sanitat de la Generalitat ValencianaGeneralitat Valenciana (PROMETEO/2019/097)
CRUE-CSIC
ERA-NET Cofound ERA-HDHL (EU Horizon 2020 Research and Innovation Programme) (696295)
ERDF funds (OP ERDF of Comunitat Valenciana 2014-2020)
EUEuropean Commission (825546)
European Joint Programming Initiative 'A Healthy Diet for a Healthy Life' (JPI HDHL)
Generalitat ValencianaGeneralitat ValencianaEuropean CommissionGeneral Electric
Instituto de Salud Carlos III from the Spanish Ministry of Innovation and Science (CB16/10/00435)
Instituto de Salud Carlos III from the Spanish Ministry of Innovation and Science (PID2019-110906RB-I00/AEI/10.13039/501100011033)
Springer Nature
University of Valencia (UV-INV-AE-1546096)

Proyectos asociados

Nuevo biomaterial bio-activo para la regeneración de lesiones medulares

Investigador Principal: M VICTORIA MORENO MANZANO

MINISTERIO DE ECON. Y COMPET. . 2019

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