Enhanced dentate gyrus synaptic plasticity but reduced neurogenesis in a mouse model of amyloidosis.
Long-term potentiation (LTP) and neurogenesis in the dentate gyrus (DG) are correlated forms of hippocampal plasticity which share, under physiological conditions, common regulatory mechanisms. In Alzheimer's disease (AD), their alterations are potentially associated with the early cellular pathology and cognitive decline. We analyzed DG LTP and neurogenesis in B6.152H mice, an amyloid precursor protein and presenilin 2 double-transgenic mouse model of amyloidosis and observed that DG LTP was strongly enhanced before and after amyloid plaque formation. Whereas proliferation of DG neuronal progenitor cells was unchanged, survival of newborn neurons was strongly decreased already before plaque formation. As similar alteration of neurogenesis was observed in PS2APP mice without changes in DG LTP (Richards et al. 2003), this study suggests that enhanced synaptic plasticity did not rescue impaired neurogenesis, and supports decreased survival of newborn neurons as an early event associated with AD detectable even before plaque formation.
Poirier
Raphaël
R
F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Veltman
Inge
I
Pflimlin
Marie Claire
MC
Knoflach
Frédéric
F
Metzger
Friedrich
F
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000686:Amyloidosis / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002470:Cell Survival; D018891:Dentate Gyrus / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D017774:Long-Term Potentiation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000473:pathology; D055495:Neurogenesis; D009473:Neuronal Plasticity; D058225:Plaque, Amyloid / Q000503:physiopathology; D053766:Presenilin-2 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses
D016564:Amyloid beta-Protein Precursor; D053766:Presenilin-2