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

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 me... Full description

Journal Title: The Journal of neuroscience : the official journal of the Society for Neuroscience October 1, 2014, Vol.34(40), pp.13314-13325
Main Author: Wang, Baiping
Other Authors: Wang, Zilai , Sun, Lu , Yang, Li , Li, Hongmei , Cole, Allysa L , Rodriguez-Rivera, Jennifer , Lu, Hui-Chen , Zheng, Hui
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1529-2401 ; DOI: 10.1523/JNEUROSCI.2848-14.2014
Link: http://search.proquest.com/docview/1586095530/?pq-origsite=primo
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title: The amyloid precursor protein controls adult hippocampal neurogenesis through GABAergic interneurons.
format: Article
creator:
  • Wang, Baiping
  • Wang, Zilai
  • Sun, Lu
  • Yang, Li
  • Li, Hongmei
  • Cole, Allysa L
  • Rodriguez-Rivera, Jennifer
  • Lu, Hui-Chen
  • Zheng, Hui
subjects:
  • Age Factors–Genetics
  • Amyloid Beta-Protein Precursor–Metabolism
  • Animals–Deficiency
  • Basic Helix-Loop-Helix Transcription Factors–Pharmacology
  • Cells, Cultured–Physiology
  • Excitatory Amino Acid Antagonists–Cytology
  • Female–Physiology
  • Gabaergic Neurons–Drug Effects
  • Hippocampus–Genetics
  • Interneurons–Deficiency
  • Male–Genetics
  • Membrane Potentials–Metabolism
  • Mice–Genetics
  • Mice, Inbred C57bl–Physiology
  • Mice, Transgenic–Pharmacology
  • Nerve Tissue Proteins–Genetics
  • Nestin–Pharmacology
  • Neurogenesis–Deficiency
  • Sodium Channel Blockers–Deficiency
  • Synaptic Transmission
ispartof: The Journal of neuroscience : the official journal of the Society for Neuroscience, October 1, 2014, Vol.34(40), pp.13314-13325
description: 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.
language: eng
source:
identifier: E-ISSN: 1529-2401 ; DOI: 10.1523/JNEUROSCI.2848-14.2014
fulltext: fulltext
issn:
  • 15292401
  • 1529-2401
url: Link


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titleThe amyloid precursor protein controls adult hippocampal neurogenesis through GABAergic interneurons.
creatorWang, Baiping ; Wang, Zilai ; Sun, Lu ; Yang, Li ; Li, Hongmei ; Cole, Allysa L ; Rodriguez-Rivera, Jennifer ; Lu, Hui-Chen ; Zheng, Hui
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identifierE-ISSN: 1529-2401 ; DOI: 10.1523/JNEUROSCI.2848-14.2014
subjectAge Factors–Genetics ; Amyloid Beta-Protein Precursor–Metabolism ; Animals–Deficiency ; Basic Helix-Loop-Helix Transcription Factors–Pharmacology ; Cells, Cultured–Physiology ; Excitatory Amino Acid Antagonists–Cytology ; Female–Physiology ; Gabaergic Neurons–Drug Effects ; Hippocampus–Genetics ; Interneurons–Deficiency ; Male–Genetics ; Membrane Potentials–Metabolism ; Mice–Genetics ; Mice, Inbred C57bl–Physiology ; Mice, Transgenic–Pharmacology ; Nerve Tissue Proteins–Genetics ; Nestin–Pharmacology ; Neurogenesis–Deficiency ; Sodium Channel Blockers–Deficiency ; Synaptic Transmission
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descriptionImpaired 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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