title: Involvement of chondroitin 6-sulfation in temporal lobe epilepsy.
abstract: Chondroitin sulfate proteoglycans (CSPGs) are predominant components of the extracellular matrix in the central nervous system (CNS). Previously, we found an increase in the 4-sulfation/6-sulfation (4S/6S) ratio of CSPGs is required for perineuronal net (PNN) formation and results in functional maturation of parvalbumin-expressing interneurons (PV cells) and termination of the critical period in the visual cortex. Here, we report that chondroitin 6-sulfation and chondroitin 6-sulfation-enriched PNNs increased in the mouse cerebral cortex and hippocampus after kainic acid (KA) treatment; simultaneously, chondroitin 4-sulfation-enriched PNNs and the 4S/6S ratio decreased. Furthermore, chondroitin 6-O-sulfotransferase-1 (C6ST-1) transgenic (TG) mice, which overexpress chondroitin 6-sulfated chains and have a decreased 4S/6S ratio, were more susceptible to KA-induced seizures than wild-type mice. These results suggested that chondroitin 6-sulfation is relevant to epilepsy most probably because of dysregulated PNN formation and PV cell maturation.
authors.affiliation: Department of Biochemistry, Kobe Pharmaceutical University, Kobe 658-8558, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Yutsudo
authors.affiliation: Department of Biochemistry, Kobe Pharmaceutical University, Kobe 658-8558, Japan. Electronic address: kitagawa@kobepharma-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitagawa
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000473:pathology; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006624:Hippocampus / Q000473:pathology; D007608:Kainic Acid / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009415:Nerve Net / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010320:Parvalbumins / Q000378:metabolism; D037121:Plant Lectins / Q000378:metabolism; D034781:Receptors, N-Acetylglucosamine / Q000378:metabolism; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000097811:Carbohydrate Sulfotransferases
chemical_list: D007608:Kainic Acid; D010320:Parvalbumins; D037121:Plant Lectins; D034781:Receptors, N-Acetylglucosamine; D040121:Semaphorin-3A; D015238:Sulfotransferases; D005680:gamma-Aminobutyric Acid; D000097811:Carbohydrate Sulfotransferases; C040129:wisteria lectin; C569944:chondroitin 4-O-sulfotransferase 2, mouse
keywords: Chondroitin sulfate; Epilepsy; Kainic acid; Perineuronal nets; Proteoglycan; Wisteria floribunda agglutinin