title: The amyloid precursor protein controls adult hippocampal neurogenesis through GABAergic interneurons.
abstract: 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.
authors.affiliation: Huffington Center on Aging, Department of Molecular and Human Genetics, and huiz@bcm.edu baipingw@bcm.edu.
authors.forename: Baiping
authors.initials: B
authors.lastname: Wang
authors.affiliation: Huffington Center on Aging, Department of Molecular and Human Genetics, and.
authors.forename: Zilai
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Huffington Center on Aging.
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.affiliation: Huffington Center on Aging.
authors.forename: Li
authors.identifier: http://orcid.org/0000-0001-7448-8588
authors.initials: L
authors.lastname: Yang
authors.affiliation: Huffington Center on Aging.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Li
authors.affiliation: Huffington Center on Aging.
authors.forename: Allysa L
authors.initials: AL
authors.lastname: Cole
authors.affiliation: Huffington Center on Aging.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rodriguez-Rivera
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, and The Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas 77030.
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Lu
authors.affiliation: Huffington Center on Aging, Department of Molecular and Human Genetics, and huiz@bcm.edu baipingw@bcm.edu.
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
mesh_terms: D000367:Age Factors; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency; D002478:Cells, Cultured; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D059330:GABAergic Neurons / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology*; D007395:Interneurons / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000172:deficiency; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D009435:Synaptic Transmission / Q000235:genetics; D013779:Tetrodotoxin / Q000494:pharmacology; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000172:deficiency
chemical_list: D016564:Amyloid beta-Protein Precursor; D051792:Basic Helix-Loop-Helix Proteins; D018691:Excitatory Amino Acid Antagonists; D009419:Nerve Tissue Proteins; D064231:Nestin; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C577485:Nes protein, mouse; C110701:Neurod6 protein, mouse; C492244:Viaat protein, mouse
keywords: Alzheimer's disease; GABAergic; adult neurogenesis; amyloid precursor protein; hippocampus; interneurons