Facilitation of learning and long-term ventral pallidal-cortical cholinergic activation by proteoglycan biglycan and chondroitin sulfate C.

We have shown previously in the rat that biglycan, a recently discovered chondroitin sulfate proteoglycan, has neurotrophic effects which are mediated by its chondroitin/dermatan sulfate chains. Here we report that biglycan has neurochemical effects when injected into the nucleus basalis magnocellularis of the ventral pallidum, a site of dense cholinergic cell bodies. The effects on the cholinergic output in the frontal cortex are long lasting, indicating profound neuroactive function akin to that expected of a long-acting hormone. Injected into the same area of the brain, as well as into the ventricles in behaviorally impaired old animals, we found that biglycan can improve learning and memory in several behavioral paradigms. Furthermore, we show that both the neurochemical effectiveness as well as the promotion of learning is carried not by the proteoglycan per se, but rather by its chondroitin sulfate moiety, thus, demonstrating for the first time memory-promoting and neuroactive effects of a glycosaminoglycan, namely, chondroitin sulfate C. The results suggest that biglycan and other extracellular matrix molecules can have neurobehavioral and pharmacological functions for beyond those traditionally attributed to this class of molecules.