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Decreased adult hippocampal neurogenesis in the PDAPP mouse model of Alzheimer's disease
Author(s) -
Donovan Michael H.,
Yazdani Umar,
Norris Rebekah D.,
Games Dora,
German Dwight C.,
Eisch Amelia J.
Publication year - 2006
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.20840
Subject(s) - neurogenesis , subgranular zone , dentate gyrus , hippocampal formation , biology , neuroscience , granule cell , neural stem cell , doublecortin , endocrinology , microbiology and biotechnology , subventricular zone , stem cell
Abnormal subgranular zone (SGZ) neurogenesis is proposed to contribute to Alzheimer's disease (AD)‐related decreases in hippocampal function. Our goal was to examine hippocampal neurogenesis in the PDAPP mouse, a model of AD with age‐dependent accumulation of amyloid‐β 42 (Aβ 42 )‐containing plaques that is well studied with regard to AD therapies. A secondary goal was to determine whether altered neurogenesis in the PDAPP mouse is associated with abnormal maturation or number of mature cells. A tertiary goal was to provide insight into why hippocampal neurogenesis appears to be increased in AD post‐mortem tissue and decreased in most AD mouse models. We report an age‐dependent decrease in SGZ proliferation in homozygous PDAPP mice. At 1 year of age, PDAPP mice also had new dentate gyrus granule neurons with abnormal maturation and fewer dying cells relative to control mice. In contrast to decreased SGZ cell birth, PDAPP mice had increased birth of immature neurons in the outer portion of the granule cell layer (oGCL), providing insight into why some studies link AD with increased neurogenesis. However, these ectopic oGCL cells were still rare compared with SGZ proliferating cells, emphasizing that the primary characteristic of PDAPP mice is decreased neurogenesis. The decrease in SGZ neurogenesis was not associated with an age‐dependent loss of dentate granule neurons. The altered neurogenesis in the PDAPP mouse may contribute to the age‐related cognitive deficits reported in this model of AD and may be a useful adjunct target for assessing the impact of AD therapies. J. Comp. Neurol. 495:70–83, 2006. © 2006 Wiley‐Liss, Inc.