Chondroitin sulfate proteoglycans (CSPGs) are the main active component of perineuronal nets (PNNs). Digestion of the glycosaminoglycan chains of CSPGs with chondroitinase ABC or transgenic attenuation of PNNs leads to prolongation of object recognition memory and activation of various forms of plasticity in the adult central nervous system. The inhibitory properties of the CSPGs depend on the pattern of sulfation of their glycosaminoglycans, with chondroitin 4-sulfate (C4S) being the most inhibitory form. In this study, we tested a number of candidates for functional blocking of C4S, leading to selection of an antibody, Cat316, which specifically recognizes C4S and blocks its inhibitory effects on axon growth. It also partly blocks binding of semaphorin 3A to PNNs and attenuates PNN formation. We asked whether injection of Cat316 into the perirhinal cortex would have the same effects on memory as chondroitinase ABC treatment. We found that masking C4S with the Cat316 antibody extended long-term object recognition memory in normal wild-type mice to 24 hours, similarly to chondroitinase or transgenic PNN attenuation. We then tested Cat316 for restoration of memory in a neurodegeneration model. Mice expressing tau with the P301S mutation showed profound loss of object recognition memory at 4 months of age. Injection of Cat316 into the perirhinal cortex normalized object recognition at 3 hours in P301S mice. These data indicate that Cat316 binding to C4S in the extracellular matrix can restore plasticity and memory in the same way as chondroitinase ABC digestion. Our results suggest that antibodies to C4S could be a useful therapeutic to restore memory function in neurodegenerative disorders.

• Klíčová slova
• Alzheimer's disease, CSPGs, Object recognition memory, Perineuronal nets, Plasticity,
• MeSH
• Alzheimerova nemoc farmakoterapie   etiologie   patofyziologie   psychologie   MeSH
• antigeny imunologie   metabolismus   fyziologie   MeSH
• cílená molekulární terapie MeSH
• extracelulární matrix metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• neurodegenerativní nemoci farmakoterapie   etiologie   patofyziologie   psychologie   MeSH
• neuroplasticita MeSH
• neutralizující protilátky terapeutické užití   MeSH
• paměť fyziologie   MeSH
• potkani Sprague-Dawley MeSH
• proteoglykany imunologie   metabolismus   fyziologie   MeSH
• protilátky aplikace a dávkování   MeSH
• reakční čas MeSH
• tauopatie komplikace   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny MeSH
• Cat316 antibody MeSH Prohlížeč
• chondroitin sulfate proteoglycan 4 MeSH Prohlížeč
• neutralizující protilátky MeSH
• proteoglykany MeSH
• protilátky MeSH