Interleukin-21 expression in hippocampal astrocytes is enhanced following kainic acid-induced seizures.
OBJECTIVE
Interleukin-21 (IL-21) is a cytokine that is an important modulator of immune responses. However, its roles in epilepsy are not completely clear. Here, we investigated the expression and distribution of IL-21 in a kainic acid (KA)-induced acute seizure mouse model.


METHODS
Mice (n = 146) were randomly divided into an age-matched group, PBS injection group, and a KA injection group. The KA-injected mice were evaluated at 1, 3, and 24 h post-injection. IL-21 mRNA and protein expression levels were measured using RT-PCR and western blotting. Immunohistochemistry and immunofluorescence staining were performed to further characterize the pattern and distribution of IL-21 expression.


RESULTS
The IL-21 mRNA and protein expression levels in the hippocampal tissues of the KA-treated mice were significantly increased as early as 1 h compared with the age-matched mice and PBS-treated mice. After this time point, the expression was reduced, but it remained higher than the level in the PBS-treated mice (p < 0.01). Immunohistochemical staining showed that IL-21 expression was distributed throughout the hippocampus, including areas CA1 and CA3, the dentate gyrus and the hilus. Moreover, immunofluorescence further showed that in the hippocampi of the KA-treated mice, IL-21 was mainly expressed in GFAP-positive astrocytes rather than in NeuN-positive neurons or CD11b-positive microglia.


CONCLUSIONS
Our data suggest that an increase in astrocyte-derived IL-21 expression in hippocampal subregions following KA-induced seizures may have potent regulatory effects on epileptogenesis.
a Department of Neurology , Xinqiao Hospital, Third Military Medical University , Chongqing , China.
Xiao-Yi
XY
Xiong
b Department of Emergency Medicine , Southwest Hospital, the Third Military Medical University , Chongqing , China.
Ting-Gang
TG
Wang
c Department of Neurosurgery , Xinqiao Hospital, Third Military Medical University , Chongqing , China.
Mei-Hua
MH
Yang
a Department of Neurology , Xinqiao Hospital, Third Military Medical University , Chongqing , China.
Zhao-You
ZY
Meng
a Department of Neurology , Xinqiao Hospital, Third Military Medical University , Chongqing , China.
Qing-Wu
QW
Yang
a Department of Neurology , Xinqiao Hospital, Third Military Medical University , Chongqing , China.
Fa-Xiang
FX
Wang
D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D007608:Kainic Acid / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced* / Q000473:pathology; D013997:Time Factors; D000098546:Interleukin-21
D039481:CD11b Antigen; D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D007378:Interleukins; D012333:RNA, Messenger; D010751:Phosphopyruvate Hydratase; D000098546:Interleukin-21; D007608:Kainic Acid
Astrocyte; Inflammatory cytokines; Interleukin-21; Kainic acid; Seizures