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The amyloid precursor protein controls adult hippocampal neurogenesis through
GABAergic interneurons
#MMPMID25274811
Wang B
; Wang Z
; Sun L
; Yang L
; Li H
; Cole AL
; Rodriguez-Rivera J
; Lu HC
; Zheng H
J Neurosci
2014[Oct]; 34
(40
): 13314-25
PMID25274811
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Impaired neurogenesis in the adult hippocampus has been implicated in AD
pathogenesis. Here we reveal that the APP plays an important role in the neural
progenitor proliferation and newborn neuron maturation in the mouse dentate
gyrus. APP controls adult neurogenesis through a non cell-autonomous mechanism by
GABAergic neurons, as selective deletion of GABAergic, but not glutamatergic, APP
disrupts adult hippocampal neurogenesis. APP, highly expressed in the majority of
GABAergic neurons in the dentate gyrus, enhances the inhibitory tone to granule
cells. By regulating both tonic and phasic GABAergic inputs to dentate granule
cells, APP maintains excitatory-inhibitory balance and preserves cognitive
functions. Our studies uncover an indispensable role of APP in the GABAergic
system for controlling adult hippocampal neurogenesis, and our findings indicate
that APP dysfunction may contribute to impaired neurogenesis and cognitive
decline associated with AD.
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