Alterations in expression of Cat‐315 epitope of perineuronal nets during normal ageing, and its modulation by an open‐channel NMDA receptor blocker, memantine
The perineuronal net (PNN) is a specialized organization of the extracellular matrix (ECM), which is enriched in chondroitin sulfate proteoglycan (CSPGs) consisting of core proteins, glycoforms, and hyaluronans (Giamanco & Matthews, 2012). Research conducted in the last two decades has indicated that PNNs play a critical role in regulation of neuronal development (Bandtlow & Zimmermann, 2000; Wang & Fawcett, 2012) and neuroprotection against oxidative stress (Cabungcal et al., 2013; Morawski, Bruckner, Riederer, Bruckner, & Arendt, 2004). Lecticans are a family of CSPGs characterized by the presence of a C‐type lectin domain in their core proteins (Iozzo, 1998); these include aggrecan, versican, neurocan, and brevican (Nakamura et al., 2000; Ruoslahti, 1996; Yamaguchi, 2000). Among these, aggrecan is thought to be critically associated with the formation of PNNs (Bruckner et al., 1993; Matthews et al., 2002; Morawski, Bruckner, Arendt, & Matthews, 2012).
A plant lectin, Wisteria floribunda agglutinin (WFA), is widely used to detect PNNs. It has been demonstrated that WFA binds to N‐acetylgalactosamine residues of CSPGs on aggrecan (Giamanco, Morawski, & Matthews, 2010). A mouse monoclonal antibody Cat‐315 is also often used to detect PNNs. This antibody was originally made to recognize the CSPGs expressed on PNNs around specific subsets of neurons (Lander, Kind, Maleski, & Hockfield, 1997). Subsequent studies have shown that Cat‐315 antibody recognizes human natural killer‐1 (HNK‐1) glycan on aggrecan‐based PNNs (Matthews et al., 2002; McHugh, Niewoehner, Rawlins, & Bannerman, 2008). Intriguingly, the patterns of distributions of WFA and Cat‐315 labeling are not always consistent with each other, for example, rat superior olivary complex (Myers, Ray, & Kulesza, 2012). In addition, modulation of neuronal activity by sensory deprivation alters formation of Cat‐315‐positive (Cat‐315+) PNNs, but not WFA+ PNNs, in the mouse barrel cortex (Czeh & Lucassen, 2007). These findings indicate that the molecular heterogeneity should be more carefully taken into account in the research of PNNs.
We have recently reported the age‐related alterations in formation of WFA+ PNNs in the mouse hippocampus (Yamada & Jinno, 2013). However, the molecular changes of PNNs in the normally ageing brain remain largely unclear. In this study, we examined the age‐related molecular changes of PNNs in the mouse hippocampus using Cat‐315 antibody, and test whether modulation of neuronal activity by an open‐channel blocker of NMDA receptor, memantine, may affect Cat‐315 epitope. Our findings indicate the alterations in molecular characteristics of hippocampal PNNs during normal brain ageing, and also suggest the potential modulation of expression levels of Cat‐315 by memantine via regulation of its subcellular localization.