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.
Highlights
Two neurogenic regions are present in the postnatal anterior brain: the ventricular- subventricular area of the lateral ventricles (V-SVZ) and the subgranular layer of the dentate gyrus of the hippocampus [1]
DNA damage could be probably caused by the broadly demonstrated capacity of Aβ of increasing reactive oxygen species (ROS) production [35]. γH2AX is a marker of replicative senescence, cellular response to damaging stress characterized by a non-proliferative but viable state [36–38]
In our study we have observed that direct microinjection of Aβ inside the lateral ventricles increases the β-gal activity in V-SVZ cells, an established marker of senescence
Summary
Two neurogenic regions are present in the postnatal anterior brain: the ventricular- subventricular area of the lateral ventricles (V-SVZ) and the subgranular layer of the dentate gyrus of the hippocampus [1]. In these regions, cell divisions continue to occur throughout life. Type C cells are large cells with invaginated nuclei and immature ultrastructural characteristics They are considered as ‘transit amplifying progenitors’ giving rise rapidly to migratory or type A cells. These cells are responsible for the formation of the granular and periglomerular neurons in the olfactory bulb [7]. Cellular migration has been described to other regions such as the striatum, corpus callosum and nucleus accumbens [8–10]
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