Potential roles of D-serine and serine racemase in experimental temporal lobe epilepsy.
To confirm the roles of D-serinergic gliotransmission in epilepsy, we investigated the relationship between spatiotemporally specific glial responses and the D-serine/serine racemase system in mesial temporal structures following status epilepticus (SE). In control animals, D-serine and serine racemase immunoreactivities were detected mainly in astrocytes. After SE, D-serine and serine racemase immunoreactivities were increased in astrocytes. Double-immunofluorescence study revealed that up-regulation of serine racemase immunoreactivity was relevant not to D-serine immunoreactivity but to nestin or vimentin immunoreactivity. Neither D-serine nor serine racemase was found in naïve or reactive microglia. In addition, phosphorylated N-methyl-D-aspartate (NMDA) receptor subunit 1 (pNR1-Ser896) immunoreactivity in the hippocampus was increased compared with controls. Increased D-serine immunoreactivity showed direct correlation with the phosphorylation of Ser896 of NR1. Given the findings of our previous study, these findings suggest that D-serine and serine racemase in astrocytes may play roles in neuronal hyperexcitability via a cooperative activation of NMDA receptors. Furthermore, serine racemase may be involved in migration and differentiation of immature astrocytes, which is relevant to reactive astrogliosis.
Ryu
H J
HJ
Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chunchon, Kangwon-Do, Republic of Korea.
Kim
J-E
JE
Yeo
S-I
SI
Kim
D-S
DS
Kwon
O-S
OS
Choi
S Y
SY
Kang
T-C
TC
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D004594:Electrophysiology; D004833:Epilepsy, Temporal Lobe / Q000201:enzymology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D007150:Immunohistochemistry; D009457:Neuroglia / Q000201:enzymology / Q000378:metabolism; D019998:Racemases and Epimerases / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012640:Seizures / Q000378:metabolism / Q000503:physiopathology; D012694:Serine / Q000502:physiology*; D000099300:Serine Racemase
D005904:Glial Fibrillary Acidic Protein; D019998:Racemases and Epimerases; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D000099300:Serine Racemase