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Publication : The amyloid precursor protein controls adult hippocampal neurogenesis through GABAergic interneurons.

First Author  Wang B Year  2014
Journal  J Neurosci Volume  34
Issue  40 Pages  13314-25
PubMed ID  25274811 Mgi Jnum  J:216597
Mgi Id  MGI:5609081 Doi  10.1523/JNEUROSCI.2848-14.2014
Citation  Wang B, et al. (2014) The amyloid precursor protein controls adult hippocampal neurogenesis through GABAergic interneurons. J Neurosci 34(40):13314-25
abstractText  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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