Abstract
Chondroitin sulfate (CS) is an important glycosaminoglycan and is mainly found in the extracellular matrix as CS proteoglycans. In the brain, CS proteoglycans are highly concentrated in perineuronal nets (PNNs), which surround synapses and modulate their functions. To investigate the importance of CS, we produced and precisely examined mice that were deficient in the CS synthesizing enzyme, CSGalNAcT1 (T1KO). Biochemical analysis of T1KO revealed that loss of this enzyme reduced the amount of CS by approximately 50% in various brain regions. The amount of CS in PNNs was also diminished in T1KO compared to wild-type mice, although the amount of a major CS proteoglycan core protein, aggrecan, was not changed. In T1KO, we observed abnormalities in several behavioral tests, including the open-field test, acoustic startle response, and social preference. These results suggest that T1 is important for plasticity, probably due to regulation of CS-dependent PNNs, and that T1KO is a good model for investigation of PNNs.
Highlights
Chondroitin sulfate (CS) is one of the most abundant glycosaminoglycans, which are composed of long, repeated disaccharide chains
These results suggest that T1 knockout mice (T1KO) is an important enzyme for CS synthesis in the brain
Because high levels of CS should be detected in perineuronal nets (PNNs) of WT, we histochemically examined Wisteria floribunda lectin (WFA)-labeled PNNs using diaminobenzidine (DAB) staining and fluorescent studies
Summary
Chondroitin sulfate (CS) is one of the most abundant glycosaminoglycans, which are composed of long, repeated disaccharide chains. For synthesis of CS proteoglycans (CSPGs), CS is attached to core proteins, such as aggrecan (AGR), neurocan, phosphacan, and versican. These CSPGs are mainly localized in the extracellular matrix. T1KO mice have impaired bone development and a 10% smaller body size than wild-type (WT) mice [7, 8]. They have the striking feature of rapid recovery following spinal cord injury [9]. We conclude that T1 plays an important role in supplying CS for PNN development and brain functions related to several characteristic behaviors
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