Abstract
Neurogenesis continues in the adult brain and is increased in certain pathological states. We reported recently that neurogenesis is enhanced in hippocampus of patients with Alzheimer's disease (AD). We now report that the effect of AD on neurogenesis can be reproduced in a transgenic mouse model. PDGF-APPSw,Ind mice, which express the Swedish and Indiana amyloid precursor protein mutations, show increased incorporation of BrdUrd and expression of immature neuronal markers in two neuroproliferative regions: the dentate gyrus and subventricular zone. These changes, consisting of ≈2-fold increases in the number of BrdUrd-labeled cells, were observed at age 3 months, when neuronal loss and amyloid deposition are not detected. Because enhanced neurogenesis occurs in both AD and an animal model of AD, it seems to be caused by the disease itself and not by confounding clinical factors. As neurogenesis is increased in PDGF-APPSw,Ind mice in the absence of neuronal loss, it must be triggered by more subtle disease manifestations, such as impaired neurotransmission. Enhanced neurogenesis in AD and animal models of AD suggests that neurogenesis may be a compensatory response and that measures to enhance neurogenesis further could have therapeutic potential.
| Original language | English |
|---|---|
| Pages (from-to) | 13363-13367 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 101 |
| Issue number | 36 |
| DOIs | |
| State | Published - 7 Sep 2004 |
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Enhanced neurogenesis in Alzheimer's disease transgenic (PDGF-APP Sw,Ind) mice. / Jin, Kunlin; Galvan, Veronica; Xie, Lin; Mao, Xiao Ou; Gorostiza, Olivia F.; Bredesen, Dale E.; Greenberg, David A.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 36, 07.09.2004, p. 13363-13367.Research output: Contribution to journal › Article
TY - JOUR
T1 - Enhanced neurogenesis in Alzheimer's disease transgenic (PDGF-APP Sw,Ind) mice
AU - Jin, Kunlin
AU - Galvan, Veronica
AU - Xie, Lin
AU - Mao, Xiao Ou
AU - Gorostiza, Olivia F.
AU - Bredesen, Dale E.
AU - Greenberg, David A.
PY - 2004/9/7
Y1 - 2004/9/7
N2 - Neurogenesis continues in the adult brain and is increased in certain pathological states. We reported recently that neurogenesis is enhanced in hippocampus of patients with Alzheimer's disease (AD). We now report that the effect of AD on neurogenesis can be reproduced in a transgenic mouse model. PDGF-APPSw,Ind mice, which express the Swedish and Indiana amyloid precursor protein mutations, show increased incorporation of BrdUrd and expression of immature neuronal markers in two neuroproliferative regions: the dentate gyrus and subventricular zone. These changes, consisting of ≈2-fold increases in the number of BrdUrd-labeled cells, were observed at age 3 months, when neuronal loss and amyloid deposition are not detected. Because enhanced neurogenesis occurs in both AD and an animal model of AD, it seems to be caused by the disease itself and not by confounding clinical factors. As neurogenesis is increased in PDGF-APPSw,Ind mice in the absence of neuronal loss, it must be triggered by more subtle disease manifestations, such as impaired neurotransmission. Enhanced neurogenesis in AD and animal models of AD suggests that neurogenesis may be a compensatory response and that measures to enhance neurogenesis further could have therapeutic potential.
AB - Neurogenesis continues in the adult brain and is increased in certain pathological states. We reported recently that neurogenesis is enhanced in hippocampus of patients with Alzheimer's disease (AD). We now report that the effect of AD on neurogenesis can be reproduced in a transgenic mouse model. PDGF-APPSw,Ind mice, which express the Swedish and Indiana amyloid precursor protein mutations, show increased incorporation of BrdUrd and expression of immature neuronal markers in two neuroproliferative regions: the dentate gyrus and subventricular zone. These changes, consisting of ≈2-fold increases in the number of BrdUrd-labeled cells, were observed at age 3 months, when neuronal loss and amyloid deposition are not detected. Because enhanced neurogenesis occurs in both AD and an animal model of AD, it seems to be caused by the disease itself and not by confounding clinical factors. As neurogenesis is increased in PDGF-APPSw,Ind mice in the absence of neuronal loss, it must be triggered by more subtle disease manifestations, such as impaired neurotransmission. Enhanced neurogenesis in AD and animal models of AD suggests that neurogenesis may be a compensatory response and that measures to enhance neurogenesis further could have therapeutic potential.
UR - http://www.scopus.com/inward/record.url?scp=4444269849&partnerID=8YFLogxK
U2 - 10.1073/pnas.0403678101
DO - 10.1073/pnas.0403678101
M3 - Article
C2 - 15340159
AN - SCOPUS:4444269849
VL - 101
SP - 13363
EP - 13367
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 36
ER -