title: Degenerative abnormalities in transgenic neocortical neuropeptide Y interneurons expressing tau-green fluorescent protein.
abstract: The introduction of a reporter gene into bacterial artificial chromosome (BAC) constructs allows a rapid identification of the cell type expressing the gene of interest. Here we used BAC transgenic mice expressing a tau-sapphire green fluorescent protein (GFP) under the transcriptional control of the neuropeptide Y (NPY) genomic sequence to characterize morphological and electrophysiological properties of NPY-GFP interneurons of the mouse juvenile primary somatosensory cortex. Electrophysiological whole-cell recordings and biocytin injections were performed to allow the morphological reconstruction of the recorded neurons in three dimensions. Ninety-six recorded NPY-GFP interneurons were compared with 39 wild-type (WT) NPY interneurons, from which 23 and 19 were reconstructed, respectively. We observed that 91% of the reconstructed NPY-GFP interneurons had developed an atypical axonal swelling from which emerge numerous ramifications. These abnormalities were very heterogeneous in shape and size. They were immunoreactive for the microtubule-associated protein tau and the lysosomal-associated membrane protein 1 (LAMP1). Moreover, an electron microscopic analysis revealed the accumulation of numerous autophagic and lysosomal vacuoles in swollen axons. Morphological analyses of NPY-GFP interneurons also indicated that their somata were smaller, their entire dendritic tree was thickened and presented a restricted spatial distribution in comparison with WT NPY interneurons. Finally, the morphological defects observed in NPY-GFP interneurons appeared to be associated with alterations of their electrophysiological intrinsic properties. Altogether, these results demonstrate that NPY-GFP interneurons developed dystrophic axonal swellings and severe morphological and electrophysiological defects that could be due to the overexpression of tau-coupled reporter constructs.
authors.affiliation: Laboratoire de Neurobiologie, CNRS UMR 7637, ESPCI ParisTech, Paris, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Rancillac
authors.forename: Jeanne
authors.initials: J
authors.lastname: Lainé
authors.forename: Quentin
authors.initials: Q
authors.lastname: Perrenoud
authors.forename: Hélène
authors.initials: H
authors.lastname: Geoffroy
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ferezou
authors.forename: Tania
authors.initials: T
authors.lastname: Vitalis
authors.forename: Jean
authors.initials: J
authors.lastname: Rossier
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D003712:Dendrites / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D066298:In Vitro Techniques; D007395:Interneurons / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000503:physiopathology*; D009478:Neuropeptide Y / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013003:Somatosensory Cortex / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D008164:Luminescent Proteins; D008239:Lysine; D051907:Lysosomal Membrane Proteins; D009478:Neuropeptide Y; D016875:tau Proteins; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C013411:biocytin