title: GABAergic hyperinnervation of dentate granule cells in the Ts65Dn mouse model of down syndrome: Exploring the role of App.
abstract: It has been suggested that increased GABAergic innervation in the hippocampus plays a significant role in cognitive dysfunction in Down syndrome (DS). Bolstering this notion, are studies linking hyper-innervation of the dentate gyrus (DG) by GABAergic terminals to failure in LTP induction in the Ts65Dn mouse model of DS. Here, we used extensive morphometrical methods to assess the status of GABAergic interneurons in the DG of young and old Ts65Dn mice and their 2N controls. We detected an age-dependent increase in GABAergic innervation of dentate granule cells (DGCs) in Ts65Dn mice. The primary source of GABAergic terminals to DGCs somata is basket cells (BCs). For this reason, we assessed the status of these cells and found a significant increase in the number of BCs in Ts65Dn mice compared with controls. Then we aimed to identify the gene/s whose overexpression could be linked to increased number of BCs in Ts65Dn and found that deleting the third copy of App gene in Ts65Dn mice led to normalization of the number of BCs in these mice. Our data suggest that App overexpression plays a major role in the pathophysiology of GABAergic hyperinnervation of the DG in Ts65Dn mice. © 2016 Wiley Periodicals, Inc.
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, California.|Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California.
authors.forename: Fatemeh S
authors.initials: FS
authors.lastname: Mojabi
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, California.|Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California.
authors.forename: Atoossa
authors.initials: A
authors.lastname: Fahimi
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, California.
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Moghadam
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, California.
authors.forename: Sarah
authors.initials: S
authors.lastname: Moghadam
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, California.|Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California.
authors.forename: M
authors.initials: M
authors.lastname: Windy McNerneny
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, California.
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Ponnusamy
authors.affiliation: Department of Neurosciences, University of California, San Diego, California.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kleschevnikov
authors.affiliation: Department of Neurosciences, University of California, San Diego, California.
authors.forename: William C
authors.initials: WC
authors.lastname: Mobley
authors.affiliation: VA Palo Alto Health Care System, Palo Alto, California.|Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Salehi
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000378:metabolism / Q000473:pathology*; D059330:GABAergic Neurons / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010320:Parvalbumins / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D051360:Cyclin-Dependent Kinase 5; D010320:Parvalbumins; D018092:Kainic Acid Receptors; D005680:gamma-Aminobutyric Acid; C495906:Cdk5 protein, mouse
keywords: GABA; Ts65Dn; basket cells; down syndrome; parvalbumin