The expression of keratan sulfate reveals a unique subset of microglia in the mouse hippocampus after pilocarpine‐induced status epileptics

• Published in: Journal of comparative neurology (1911) Vol. 528; no. 1; pp. 14 - 31
• Main Authors: Ohgomori, Tomohiro, Jinno, Shozo
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-01-2020; Wiley Subscription Services, Inc
• Subjects: Animal models; Cytokines; Epilepsy; Epitopes; Hippocampus; Inflammation; Keratan sulfate; Latent period; Microglia; Neurological diseases; Phagocytes; Phagocytosis; Pilocarpine; Presynapse; Rodents; RRID:AB_10549463; RRID:AB_1732087; RRID:AB_2224402; RRID:AB_2307351; RRID:AB_2340476; RRID:AB_2340593; RRID:AB_2340792; RRID:AB_2571618; RRID:AB_2736983; RRID:AB_2783552; RRID:AB_2800343; RRID:AB_312788; RRID:AB_312794; RRID:AB_394657; RRID:AB_395252; RRID:AB_477019; RRID:AB_893678; RRID:SCR_017071; epilepsy; RRID:AB_312794; phagocytosis; hippocampus; RRID:AB_2800343; RRID:AB_394657; RRID:AB_2340792; RRID:AB_2736983; RRID:AB_10549463; RRID:AB_477019; RRID:AB_2340476; RRID:AB_2307351; RRID:AB_2340593; RRID:AB_1732087; RRID:AB_2571618; RRID:AB_395252; RRID:AB_893678; keratan sulfate; RRID:AB_2224402; RRID:AB_2783552; RRID:SCR_017071; microglia; RRID:AB_312788
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.24734

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.
The role of microglia expressing the 5D4 epitope, a marker of keratan sulfate, was examined using mouse model of pilocarpine‐induced status epilepticus (SE). No microglia expressing the 5D4 epitope were found in the hippocampus at 1 day after SE onset (PILO‐1d), but they were scattered at 14 days post‐SE (PILO‐14d). The phagocytosis activity and the ratio of microglia‐synapse contact were higher in 5D4‐positive cells than in 5D4‐negative cells. Microglia expressing the 5D4 epitope may thus be engaged in synaptic pruning during the latent period after SE.