Chondroitin sulfate proteoglycan-5 forms perisynaptic matrix assemblies in the adult rat cortex

Composition of the brain extracellular matrix changes in time as maturation proceeds. Chondroitin sulfate proteoglycan 5 (CSPG-5), also known as neuroglycan C, has been previously associated to differentiation since it shapes neurite growth and synapse forming. Here, we show that this proteoglycan persists in the postnatal rat brain, and its expression is higher in cortical regions with plastic properties, including hippocampus and the medial prefrontal cortex at the end of the second postnatal week. Progressively accumulating after birth, CSPG-5 typically concentrates around glutamatergic and GABAergic terminals in twelve-week old rat hippocampus. CSPG-5-containing perisynaptic matrix rings often appear at the peripheral margin of perineuronal nets. Electron microscopy and analysis of synaptosomal fraction showed that CSPG-5 accumulates around, and is associated to synapses, respectively. In vitro analyses suggest that neurons, but less so astrocytes, express CSPG-5 in rat primary neocortical cultures, and CSPG-5 produced by transfected neuroblastoma cells appear at endings and contact points of neurites. In human subjects, CSPG-5 expression shifts in brain areas of the default mode network of suicide victims, which may reflect an impact in the pathogenesis of psychiatric diseases or support diagnostic power.