title: Alterations in expression of Cat-315 epitope of perineuronal nets during normal ageing, and its modulation by an open-channel NMDA receptor blocker, memantine.
abstract: The perineuronal net (PNN), a specialized aggregate of the extracellular matrix, is involved in neuroprotection against oxidative stress, which is now recognized as a major contributor to age-related decline in brain functions. In this study, we investigated the age-related molecular changes of PNNs using monoclonal antibody Cat-315, which recognizes human natural killer-1 (HNK-1) glycan on aggrecan-based PNNs. Western blot analysis showed that the expression levels of Cat-315 epitope in the hippocampus were higher in middle-aged (MA, 12-month-old) mice than in young adult (YA, 2-month-old) mice. Although there were no differences in the expression levels of Cat-315 epitope between old age (OA, 20-month-old) and MA mice, Cat-315 immunoreactivity was also detected in astrocytes of OA mice. To focus on Cat-315 epitope in PNNs, we used YA and MA mice in the following experiments. Optical disector analysis showed that there were no differences in the numbers of Cat-315-positive (Cat-315+) PNNs between YA and MA mice. Fluorescence intensity analysis indicated that Cat-315 immunoreactivity in PNNs increased with age in the dorsal hippocampus, which is mainly involved in cognitive functions. Administration of an open-channel blocker of NMDA receptor, memantine, reduced the expression levels of Cat-315 epitope in the hippocampus. Furthermore, the numbers of glutamatergic and GABAergic terminals colocalized with Cat-315 epitope around parvalbumin-positive neurons were decreased by memantine. These findings provide novel insight into the involvement of PNNs in normal brain ageing, and suggest that memantine may counteract the age-related alterations in expression levels of Cat-315 epitope via regulation of its subcellular localization.
authors.affiliation: Department of Anatomy and Neuroscience, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Yamada
authors.affiliation: Department of Anatomy and Neuroscience, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ohgomori
authors.affiliation: Department of Anatomy and Neuroscience, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
authors.forename: Shozo
authors.identifier: http://orcid.org/0000-0002-7596-8118
authors.initials: S
authors.lastname: Jinno
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D018959:CD57 Antigens / Q000276:immunology / Q000378:metabolism*; D002452:Cell Count; D000939:Epitopes / Q000276:immunology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D018959:CD57 Antigens; D000939:Epitopes; D018691:Excitatory Amino Acid Antagonists; D010320:Parvalbumins; D064568:S100 Calcium Binding Protein beta Subunit; D050598:Vesicular Glutamate Transport Protein 1; D005968:Glutamate Decarboxylase; D008559:Memantine
keywords: Cat-315; RRID: AB_94270; RRID:AB_2336938; RRID:AB_2571616; RRID:AB_2571878; ageing; hippocampus; memantine; perineuronal nets