heparitin-sulfate and Epilepsy

Mucopolysaccharidosis (MPS) disorders are caused by deficiencies in lysosomal enzymes, leading to impaired glycosaminoglycan (GAG) degradation. The resulting GAG accumulation in cells and connective tissues ultimately results in widespread tissue and organ dysfunction. The seven MPS types currently described are heterogeneous and progressive disorders, with somatic and neurological manifestations depending on the type of accumulating GAG. Heparan sulfate (HS) is one of the GAGs stored in patients with MPS I, II, and VII and the main GAG stored in patients with MPS III. These disorders are associated with significant central nervous system (CNS) abnormalities that can manifest as impaired cognition, hyperactive and/or aggressive behavior, epilepsy, hydrocephalus, and sleeping problems. This review discusses the anatomical and pathophysiological CNS changes accompanying HS accumulation as well as the mechanisms believed to cause CNS abnormalities in MPS patients. The content of this review is based on presentations and discussions on these topics during a meeting on the brain in MPS attended by an international group of MPS experts.

Topics: Brain; Cognitive Dysfunction; Epilepsy; Heparitin Sulfate; Humans; Mucopolysaccharidoses

Proteoglycans and glycosaminoglycans are elements of matrix. In the nervous system, glycosaminoglycans modulate neurite outgrowth and are co-receptors for growth factors playing a crucial role in cell differentiation and synaptogenesis. The receptor of protein tyrosine phosphatase beta (RPTPbeta) is a chondroitin sulphate proteoglycan which plays an important role in neural morphogenesis and axon guidance mechanisms. Pilocarpine-treated rats present status epilepticus, which is followed by a seizure-free period (silent), by a period of spontaneous recurrent seizures (chronic), and the hippocampus of these animals exhibits cell loss and mossy fiber sprouting. Thus, the synthesis of heparan sulphate and chondroitin sulphate and the time course of RPTPbeta immunoreactivity were studied in the hippocampus and cerebral cortex during these phases of pilocarpine-induced epilepsy. The results showed decreased synthesis of heparan sulphate during the acute phase and an increased synthesis of chondroitin sulphate during the silent period in the cortex and hippocampus. In control rats RPTPbeta immunoreactivity was detected only in glial cells. After 6 h of status epilepticus the RPTPbeta immunoreactivity was no longer detectable in the glial cells in both tissues and intense staining became evident in the matrix, surrounding CA3 and dentate gyrus and piriform cortex neurones. In the silent and chronic periods RPTPbeta immunoreactivity was mainly detected in neuronal somata and fibers of neurones of hippocampus and cortex. These changes show a selective variation of synthesis and expression of glycosaminoglycans and RPTPbeta in relation to epilepsy suggesting a molecular interplay between glia and neurones during seizures.

Topics: Animals; Cerebral Cortex; Chondroitin Sulfates; Epilepsy; Glycosaminoglycans; Heparitin Sulfate; Hippocampus; Male; Nerve Tissue Proteins; Pilocarpine; Protein Tyrosine Phosphatases; Proteoglycans; Rats; Rats, Wistar; Reaction Time; Receptor-Like Protein Tyrosine Phosphatases, Class 5; Status Epilepticus