TY - JOUR
T1 - The expression of keratan sulfate reveals a unique subset of microglia in the mouse hippocampus after pilocarpine-induced status epileptics
AU - Ohgomori, Tomohiro
AU - Jinno, Shozo
N1 - Funding Information:
The authors thank Mses. Machiko Endoh and Kana Maekawa for their secretarial and technical assistance. We also thank Editage (www. editage.jp) for English language editing. We appreciate the technical assistance from the Research Support Center, Research Center for Human Disease Modeling, Kyushu University Graduate School of Medical Sciences. This work was supported in part by JSPS KAKENHI 15H04267 (to S.J.), 17K00858 (to T.O.), and 19H05022 (to S.J.).
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Induction of keratan sulfate in microglia has been found in several animal models of neurological disorders. However, the significance of keratan sulfate-expressing microglia is not fully understood. To address this issue, we analyzed the characteristics of microglia labeled by the 5D4 epitope, a marker of high-sulfated keratan sulfate, in the mouse hippocampus during the latent period after pilocarpine-induced status epilepticus (SE). Only 5D4-negative (5D4−) microglia were found in the CA1 region of vehicle-treated controls and pilocarpine-treated mice at 1 day after SE onset. A few 5D4+ microglia appeared in the strata oriens and radiatum at 5 days post-SE, and they were distributed into the stratum pyramidale at 14 days post-SE. The expressions of genes related to both anti- and pro-inflammatory cytokines were higher in 5D4+ cells than in 5D4− cells at 5 but not 14 days post-SE. The expressions of genes related to phagocytosis were higher in 5D4+ cells than in 5D4− cells throughout the latent period. The phagocytic activity of microglia, as measured by engulfment of the zymosan bioparticles, was higher in 5D4+ cells than in 5D4− cells. The contact ratios between excitatory synaptic boutons and microglia were also higher in 5D4+ cells than in 5D4− cells at 5 and 14 days post-SE. The excitatory/inhibitory ratios of synaptic boutons within the microglial domain were lower in 5D4+ cells than in 5D4− cells at 14 days post-SE. Our findings indicate that 5D4+ microglia may play some role in epileptogenesis via pruning of excitatory synapses during the latent period after SE.
AB - Induction of keratan sulfate in microglia has been found in several animal models of neurological disorders. However, the significance of keratan sulfate-expressing microglia is not fully understood. To address this issue, we analyzed the characteristics of microglia labeled by the 5D4 epitope, a marker of high-sulfated keratan sulfate, in the mouse hippocampus during the latent period after pilocarpine-induced status epilepticus (SE). Only 5D4-negative (5D4−) microglia were found in the CA1 region of vehicle-treated controls and pilocarpine-treated mice at 1 day after SE onset. A few 5D4+ microglia appeared in the strata oriens and radiatum at 5 days post-SE, and they were distributed into the stratum pyramidale at 14 days post-SE. The expressions of genes related to both anti- and pro-inflammatory cytokines were higher in 5D4+ cells than in 5D4− cells at 5 but not 14 days post-SE. The expressions of genes related to phagocytosis were higher in 5D4+ cells than in 5D4− cells throughout the latent period. The phagocytic activity of microglia, as measured by engulfment of the zymosan bioparticles, was higher in 5D4+ cells than in 5D4− cells. The contact ratios between excitatory synaptic boutons and microglia were also higher in 5D4+ cells than in 5D4− cells at 5 and 14 days post-SE. The excitatory/inhibitory ratios of synaptic boutons within the microglial domain were lower in 5D4+ cells than in 5D4− cells at 14 days post-SE. Our findings indicate that 5D4+ microglia may play some role in epileptogenesis via pruning of excitatory synapses during the latent period after SE.
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U2 - 10.1002/cne.24734
DO - 10.1002/cne.24734
M3 - Article
C2 - 31237692
AN - SCOPUS:85068448066
VL - 528
SP - 14
EP - 31
JO - Journal of Comparative Neurology
JF - Journal of Comparative Neurology
SN - 0021-9967
IS - 1
ER -