TY - JOUR
T1 - Involvement of chondroitin 6-sulfation in temporal lobe epilepsy
AU - Yutsudo, Noriko
AU - Kitagawa, Hiroshi
N1 - Funding Information:
We thank S. Nadanaka and S. Miyata for technical advice regarding GAG disaccharide analysis and immunohistochemical analysis, respectively. This work was supported in part by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) -Supported Program for the Strategic Research Foundation at Private Universities ( 2012–2016 to H.K.), MEXT Grants-in-aid for Scientific Research on Innovative Areas (No. 23110003 to H.K.), and a MEXT Scientific Research B grant (No. 25293014 to H.K.).
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84954404580&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84954404580&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2015.07.009
DO - 10.1016/j.expneurol.2015.07.009
M3 - Article
C2 - 26231575
AN - SCOPUS:84954404580
SN - 0014-4886
VL - 274
SP - 126
EP - 133
JO - Experimental Neurology
JF - Experimental Neurology
ER -