Adult Neural Stem Cell Migration Is Impaired in a Mouse Model of Alzheimer's Disease
Por:
D. ESTEVE, M. MOLINA-NAVARRO, E. GIRALDO, N. MARTINEZ-VAREA, M. BLANCO-GANDIA, M. RODRIGUEZ-ARIAS, J. GARCIA-VERDUGO, J. VINA and A. LLORET
Publicada:
1 feb 2022
Ahead of Print:
1 dic 2021
Resumen:
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.
Filiaciones:
D. ESTEVE:
Univ Valencia, Dept Physiol, Freshage Res Grp, Fac Med, Valencia, Spain
Inst Hlth Res INCLIVA, CIBERFES, Valencia, Spain
M. MOLINA-NAVARRO:
Univ Valencia, Inst Cavanilles Biodiversidad & Biol Evolut, Lab Comparat Neurobiol, CIBERNED, Valencia, Spain
:
Ctr Invest Principe Felipe, Neuronal & Tissue Regenerat Lab, Valencia, Spain
Univ Politecn Valencia, Dept Biotecnol, Valencia, Spain
N. MARTINEZ-VAREA:
Czech Acad Sci, Inst Expt Med, Prague, Czech Republic
Charles Univ Prague, Fac Med 2, Prague, Czech Republic
M. BLANCO-GANDIA:
Univ Valencia, Fac Psycol, Dept Psychobiol, Valencia, Spain
M. RODRIGUEZ-ARIAS:
Univ Valencia, Fac Psycol, Dept Psychobiol, Valencia, Spain
J. VINA:
Univ Valencia, Dept Physiol, Freshage Res Grp, Fac Med, Valencia, Spain
Inst Hlth Res INCLIVA, CIBERFES, Valencia, Spain
A. LLORET:
Univ Valencia, Dept Physiol, Freshage Res Grp, Fac Med, Valencia, Spain
Inst Hlth Res INCLIVA, CIBERFES, Valencia, Spain
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