title: Transgenic mice overexpressing reticulon 3 develop neuritic abnormalities.
abstract: Dystrophic neurites are swollen dendrites or axons recognizable near amyloid plaques as a part of important pathological feature of Alzheimer's disease (AD). We report herein that reticulon 3 (RTN3) is accumulated in a distinct population of dystrophic neurites named as RTN3 immunoreactive dystrophic neurites (RIDNs). The occurrence of RIDNs is concomitant with the formation of high-molecular-weight RTN3 aggregates in brains of AD cases and mice expressing mutant APP. Ultrastructural analysis confirms accumulation of RTN3-containing aggregates in RIDNs. It appears that the protein level of RTN3 governs the formation of RIDNs because transgenic mice expressing RTN3 will develop RIDNs, initially in the hippocampal CA1 region, and later in other hippocampal and cortical regions. Importantly, we show that the presence of dystrophic neurites in Tg-RTN3 mice causes impairments in spatial learning and memory, as well as synaptic plasticity, implying that RIDNs potentially contribute to AD cognitive dysfunction. Together, we demonstrate that aggregation of RTN3 contributes to AD pathogenesis by inducing neuritic dystrophy. Inhibition of RTN3 aggregation is likely a therapeutic approach for reducing neuritic dystrophy.
authors.affiliation: Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Xiangyou
authors.initials: X
authors.lastname: Hu
authors.forename: Qi
authors.initials: Q
authors.lastname: Shi
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Zhou
authors.forename: Wanxia
authors.initials: W
authors.lastname: He
authors.forename: Hong
authors.initials: H
authors.lastname: Yi
authors.forename: Xinghua
authors.initials: X
authors.lastname: Yin
authors.forename: Marla
authors.initials: M
authors.lastname: Gearing
authors.forename: Allan
authors.initials: A
authors.lastname: Levey
authors.forename: Riqiang
authors.initials: R
authors.lastname: Yan
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism* / Q000648:ultrastructure; D045442:Rotarod Performance Test
chemical_list: D017931:DNA Primers; D009419:Nerve Tissue Proteins; C482720:Rtn3 protein, mouse