title: Increase in α-tubulin modifications in the neuronal processes of hippocampal neurons in both kainic acid-induced epileptic seizure and Alzheimer's disease.
abstract: Neurodegeneration includes acute changes and slow-developing alterations, both of which partly involve common cellular machinery. During neurodegeneration, neuronal processes are impaired along with dysregulated post-translational modifications (PTMs) of cytoskeletal proteins. In neuronal processes, tubulin undergoes unique PTMs including a branched form of modification called glutamylation and loss of the C-terminal tyrosine residue and the penultimate glutamic acid residue forming Δ2-tubulin. Here, we investigated the state of two PTMs, glutamylation and Δ2 form, in both acute and slow-developing neurodegenerations, using a newly generated monoclonal antibody, DTE41, which had 2-fold higher affinity to glutamylated Δ2-tubulin, than to unmodified Δ2-tubulin. DTE41 recognised glutamylated Δ2-tubulin preferentially in immunostaining than in enzyme-linked immunosorbent assay and immunoblotting. In normal mouse brain, DTE41 stained molecular layer of the cerebellum as well as synapse-rich regions in pyramidal neurons of the cerebral cortex. In kainic acid-induced epileptic seizure, DTE41-labelled signals were increased in the hippocampal CA3 region, especially in the stratum lucidum. In the hippocampi of post-mortem patients with Alzheimer's disease, intensities of DTE41 staining were increased in mossy fibres in the CA3 region as well as in apical dendrites of the pyramidal neurons. Our findings indicate that glutamylation on Δ2-tubulin is increased in both acute and slow-developing neurodegeneration.
authors.affiliation: Department of Cellular and Molecular Anatomy, and International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Hang Thi
authors.initials: HT
authors.lastname: Vu
authors.affiliation: Choju Medical Institute, Fukushimura Hospital, Toyohashi, Japan.|Department of Medicine for Aging in Place and Community-Based Medical Education, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Akatsu
authors.affiliation: Choju Medical Institute, Fukushimura Hospital, Toyohashi, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hashizume
authors.affiliation: Department of Cellular and Molecular Anatomy, and International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.|Department of Systems Molecular Anatomy, Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.|Department of Anatomy, The University of Hong Kong, Hong Kong, China.|Division of Neural Systematics, National Institute for Physiological Sciences, Okazaki, Japan.|Riken Center for Molecular Imaging Science, Kobe, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Setou
authors.affiliation: Department of Cellular and Molecular Anatomy, and International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ikegami
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007608:Kainic Acid / Q000008:administration & dosage; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011689:Purkinje Cells / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D014404:Tubulin / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D014404:Tubulin; D007608:Kainic Acid