title: Lack of collagen VI promotes neurodegeneration by impairing autophagy and inducing apoptosis during aging.
abstract: Collagen VI is an extracellular matrix (ECM) protein with a broad distribution in different tissues and mostly deposited at the close periphery of the cell surface. Previous studies revealed that collagen VI protects neurons from the toxicity of amyloid-βpeptides and from UV-induced damage. However, the physiological role of this protein in the central nervous system (CNS) remains unknown. Here, we established primary neural cultures from murine cortex and hippocampus, and carried out in vitro and in vivo studies in wild-type and collagen VI null (Col6a1-/-) mice. Col6a1-/- neural cultures displayed an increased incidence of spontaneous apoptosis and higher vulnerability to oxidative stress, accompanied by altered regulation of autophagy with increased p62 protein levels and decreased LC3 lipidation. Analysis of brain sections confirmed increased apoptosis and abnormal regulation of autophagy in the CNS of collagen VI-deficient animals. To investigate the in vivo physiological consequences of these CNS defects, we carried out functional studies and found that motor and memory task performances were impaired in aged Col6a1-/-mice. These findings indicate that lack of collagen VI leads to spontaneous apoptosis and defective autophagy in neural cells, and point at a protective role for this ECM protein in the CNS during physiological aging.
authors.affiliation: Department of Molecular Medicine, University of Padova, I-35131 Padova, Italy.
authors.forename: Matilde
authors.initials: M
authors.lastname: Cescon
authors.affiliation: Department of Molecular Medicine, University of Padova, I-35131 Padova, Italy.
authors.forename: Peiwen
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Molecular Medicine, University of Padova, I-35131 Padova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Castagnaro
authors.affiliation: Department of Molecular Medicine, University of Padova, I-35131 Padova, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Gregorio
authors.affiliation: Department of Molecular Medicine, University of Padova, I-35131 Padova, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bonaldo
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D024142:Collagen Type VI / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D008568:Memory / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009048:Motor Skills / Q000502:physiology; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D024142:Collagen Type VI
keywords: aging brain; apoptosis; autophagy; collagen VI; extracellular matrix