title: Polyglutamine toxicity induces rod photoreceptor division, morphological transformation or death in spinocerebellar ataxia 7 mouse retina.
abstract: In neurodegenerative disorders caused by polyglutamine (polyQ) expansion, polyQ toxicity is thought to trigger a linear cascade of successive degenerative events leading to neuronal death. To understand how neurons cope with polyQ toxicity, we studied a Spinocerebellar ataxia 7 (SCA7) mouse which expresses polyQ-expanded ATXN7 only in rod photoreceptors. We show that in response to polyQ toxicity, SCA7 rods go through a range of radically different cell fates, including apoptotic and non-apoptotic cell death, cell migration, morphological transformation into a round cell or, most remarkably, cell division. The temporal profile of retinal remodeling indicates that some degenerative pathways are triggered early in the disease but decline later on, while others worsen progressively. Retinal remodeling results in a relative maintenance of photoreceptor population, but does not preserve the retinal function. Rod responses to proteotoxicity correlate with the nature, level and ratio of mutant ATXN7 species. The multifaceted response of neurons to polyQ toxicity is an important concept for the design of therapeutic strategies.
authors.affiliation: Department of Neurobiology and Genetics, Institute of Genetics and Molecular and Cellular Biology (IGBMC), UMR 7104-CNRS/INSERM/UdS, BP10142, 67404 Illkirch Cédex, France.
authors.forename: Marina G
authors.initials: MG
authors.lastname: Yefimova
authors.forename: Nadia
authors.initials: N
authors.lastname: Messaddeq
authors.forename: Alice
authors.initials: A
authors.lastname: Karam
authors.forename: Carine
authors.initials: C
authors.lastname: Jacquard
authors.forename: Chantal
authors.initials: C
authors.lastname: Weber
authors.forename: Laurent
authors.initials: L
authors.lastname: Jonet
authors.forename: Uwe
authors.initials: U
authors.lastname: Wolfrum
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Jeanny
authors.forename: Yvon
authors.initials: Y
authors.lastname: Trottier
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D000067719:Ataxin-7; D016923:Cell Death / Q000502:physiology; D002465:Cell Movement / Q000235:genetics; D048430:Cell Shape / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D010455:Peptides / Q000633:toxicity*; D012162:Retinal Degeneration / Q000209:etiology / Q000473:pathology*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000473:pathology*; D020754:Spinocerebellar Ataxias / Q000150:complications / Q000378:metabolism* / Q000473:pathology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000067719:Ataxin-7; C000593831:Atxn7 protein, mouse; D009419:Nerve Tissue Proteins; D010455:Peptides; C097188:polyglutamine