Overexpression of wild type but not an FAD mutant presenilin-1 promotes neurogenesis in the hippocampus of adult mice.
Mutations in the presenilin-1 (PS-1) gene are one cause of familial Alzheimer's disease (FAD). However, the functions of the PS-1 protein as well as how PS-1 mutations cause FAD are incompletely understood. Here we investigated if neuronal overexpression of wild-type or FAD mutant PS-1 in transgenic mice affects neurogenesis in the hippocampus of adult animals. We show that either a wild-type or an FAD mutant PS-1 transgene reduces the number of neural progenitors in the dentate gyrus. However, the wild-type, but not the FAD mutant PS-1 promoted the survival and differentiation of progenitors leading to more immature granule cell neurons being generated in PS-1 wild type expressing animals. These studies suggest that PS-1 plays a role in regulating neurogenesis in adult hippocampus and that FAD mutants may have deleterious properties independent of their effects on amyloid deposition.
Wen
Paul H
PH
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA.
Shao
Xiang
X
Shao
Zhiping
Z
Hof
Patrick R
PR
Wisniewski
Thomas
T
Kelley
Kevin
K
Friedrich
Victor L
VL
Ho
Lap
L
Pasinetti
Giulio M
GM
Shioi
Junichi
J
Robakis
Nikolaos K
NK
Elder
Gregory A
GA
D000375:Aging / Q000235:genetics / Q000502:physiology; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D006624:Hippocampus / Q000166:cytology* / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009154:Mutation / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D053764:Presenilin-1; D013234:Stem Cells / Q000166:cytology
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1