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.

PSA-NCAM Colocalized with Cholecystokinin-Expressing Cells in the Hippocampus Is Involved in Mediating Antidepressant Efficacy

“…Approximately 30 lines were obtained from each CCK ϩ cell. We analyzed the molecular profile of the path within 2 m from the soma to count the synaptic boutons, as reported previously (Yamada et al, 2017).…”

Structural Variation of Chondroitin Sulfate Chains Contributes to the Molecular Heterogeneity of Perineuronal Nets

“…Two monoclonal antibodies, Cat315 and Cat316, both of which react with aggrecan, label distinct but partially overlapping populations of PNNs. Cat315 recognizes the human natural killer-1 (HNK-1) glycan epitope on aggrecan (Matthews et al, 2002 ; Yabuno et al, 2015 ; Yamada et al, 2017 ). Both WFA and Cat316 are thought to bind to CS chains on aggrecan in PNNs (Brückner et al, 1998 ; Matthews et al, 2002 ; Giamanco et al, 2010 ).…”

The role of folate receptor α in the partial rejuvenation of dentate gyrus cells. Improvement of cognitive function in elderly mice

“…Taking into account the results shown in Figure 5, we suggest that neuronal signaling is enhanced through changes in excitatory (glutamatergic) [29, 36] but also in inhibitory neurons [55]. In addition, both results could be related between them, since alterations in the expression of PNN components during aging, could be modulated by alterations of NMDA function [58].…”

“…Interestingly, long-term but not short-term recognition memory was enhanced by folate treatment, as occurred with YF cyclical overexpression [36]. Furthermore, aging and age-associated diseases like Alzheimer disease have been related to an increase in perineuronal nets (PNN) in different regions of the brain, including the hippocampus, [22, 45, 50, 51, 58]. PNN are a specific type of ECM wrapped around some interneurons [55] that restrict the plasticity of these cells.…”