Format

Send to

Choose Destination
Sci Rep. 2018 Dec 18;8(1):17931. doi: 10.1038/s41598-018-36363-7.

Adult hippocampal neurogenesis occurs in the absence of Presenilin 1 and Presenilin 2.

Author information

1
Department of Cellular and Molecular Medicine, Brain and Mind Research Institute, and Neuroscience Program, University of Ottawa, Ottawa, Ontario, K1H8M5, Canada.
2
Department of Neurology, Brigham and Women's Hospital and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, 02115, USA.
3
Department of Cellular and Molecular Medicine, Brain and Mind Research Institute, and Neuroscience Program, University of Ottawa, Ottawa, Ontario, K1H8M5, Canada. dlagace@uottawa.ca.

Abstract

Mutations in the presenilin genes (PS1 and PS2) are a major cause of familial-Alzheimer's disease (FAD). Presenilins regulate neurogenesis in the developing brain, with loss of PS1 inducing aberrant premature differentiation of neural progenitor cells, and additional loss of PS2 exacerbating this effect. It is unclear, however, whether presenilins are involved in adult neurogenesis, a process that may be impaired in Alzheimer's disease within the hippocampus. To investigate the requirement of presenilins in adult-generated dentate granule neurons, we examined adult neurogenesis in the PS2-/- adult brain and then employ a retroviral approach to ablate PS1 selectively in dividing progenitor cells of the PS2-/- adult brain. Surprisingly, the in vivo ablation of both presenilins resulted in no defects in the survival and differentiation of adult-generated neurons. There was also no change in the morphology or functional properties of the retroviral-labeled presenilin-null cells, as assessed by dendritic morphology and whole-cell electrophysiology analyses. Furthermore, while FACS analysis showed that stem and progenitor cells express presenilins, inactivation of presenilins from these cells, using a NestinCreERT2 inducible genetic approach, demonstrated no changes in the proliferation, survival, or differentiation of adult-generated cells. Therefore, unlike their significant role in neurogenesis during embryonic development, presenilins are not required for cell-intrinsic regulation of adult hippocampal neurogenesis.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center