Reduced expression of MAb6B4 epitopes on chondroitin sulfate proteoglycan aggrecan in perineuronal nets from cerebral cortices of SAMP10 mice: A model for age‐dependent neurodegeneration

Abstract

The accelerated senescence-prone SAMP10 mouse strain is a model for age-dependent neurodegeneration and is characterized by brain atrophy and deficits in learning and memory. Because perineuronal nets play an important role in the synaptic plasticity of adult brains, we examined the distributions of molecules that constitute perineuronal nets in SAMP10 mouse brain samples and compared them with those in control SAMR1 mouse samples. Proteoglycan-related monoclonal antibody 6B4 (MAb6B4) clearly immunostained perineuronal nets in SAMR1 mice cortices, but the corresponding immunostaining in SAMP10 mice was very faint. MAb6B4 recognizes phosphacan/PTPzeta in immature brains. However, this antibody recognized several protein bands, including a 400-kDa core glycoprotein from chondroitin sulfate proteoglycan in homogenates of mature cortices from SAMR1 mice. The 400-kDa band was also recognized by antiaggrecan antibodies. The aggrecan core glycoprotein band was also detectable in samples from SAMP10 mice, but this glycoprotein was faintly immunostained by MAb6B4. Because MAb6B4 recognized the same set of protein bands that the monoclonal antibody Cat-315 recognized in mature cerebral cortices of SAMR1 mice, the MAb6B4 epitope appears to be closely related to that of Cat-315 and presumably represents a novel type of oligosaccharide that attaches to aggrecans. The Cat-315 epitope colocalized with aggrecan in perineuronal nets from SAMR1 mouse brain samples, whereas its expression was prominently reduced in SAMP10 mouse brain samples. The biological significance of the MAb6B4/Cat-315 epitope in brain function and its relationship to the neurodegeneration and learning disabilities observed in SAMP10 mice remain to be elucidated.

RPTPζ/phosphacan is abnormally glycosylated in a model of muscle–eye–brain disease lacking functional POMGnT1

“…While both Cat-315 and 6B4 have been shown to primarily detect carbohydrate epitopes on RPTPζ/phosphacan in the early developing brain these antibodies largely detect carbohydrate epitopes on aggrecan and PNs in the adult brain (Matthews et al, 2002; McRae et al, 2007; Saitoh et al, 2008). Given that the immunoreactivity of both Cat-315 and 6B4 on RPTPζ/phosphacan were dramatically reduced in the cortex of embryonic and early postnatal POMGnT1 knockout animals, the reactivity of these antibodies were evaluated in the cortex of adult POMGnT1 knockout animals to determine if their carbohydrate epitopes present on aggrecan were also lost in the absence of O -mannosyl linked glycans.…”

“…Previous work has shown that both Cat-315 and 6B4 primarily detect carbohydrates on RPTPζ/phosphacan early in development (Dino et al, 2006; Maeda et al, 1994) and on aggrecan in the adult brain (Matthews et al, 2002, McRae et al, 2007, Saitoh et al, 2008). Therefore, while the reactivity of these antibodies for RPTPζ/phosphacan was eliminated, surprisingly it was essentially unaffected on aggrecan localized to PN structures.…”

The Senescence-accelerated Mouse (SAM): A Higher Oxidative Stress and Age-dependent Degenerative Diseases Model

“…The SAMP10 strain of mice is a model of brain aging in which senescence is characterized by cerebral atrophy and several neurodegeneration phenotypes [46][47][48][49][50]. Recently, some molecular abnormalities have been identified in SAMP10 mice, including the absence of normal fibroblast growth factor 1 protein [51] and a reduced expression of MAb6B4 epitopes on aggrecan in perineuronal nets from the cerebral cortices [52]. However, whether these molecular alterations have a causal relationship with neurodegeneration remains to be elucidated.…”

Losing the sugar coating: Potential impact of perineuronal net abnormalities on interneurons in schizophrenia

“…The contribution of such diversity to PNN composition has been, to some extent, investigated using antibodies raised against core proteins and specific sulfation patterns (Bertolotto et al, 1996; Caterson, 2012; Hagihara et al, 1999; Haunso et al, 1999; Hayashi et al, 2007; Madinier et al, 2014; Matthews et al, 2002; Miyata et al, 2012; Nakamura et al, 2009; Ojima et al, 1998; Racz et al, 2014; Saitoh et al, 2008; Yin et al, 2006), as well as lectins such as wisteria floribunda agglutinin (WFA). WFA, perhaps the most widely used in studies of PNNs, binds specifically to N-acetyl-D-galactosamine on the terminal end of CS chains, with a preference for beta glycosidic linkage (Kurokawa et al, 1976; Young and Williams, 1985).…”