The PPARγ agonist rosiglitazone prevents neuronal loss and attenuates development of spontaneous recurrent seizures through BDNF/TrkB signaling following pilocarpine-induced status epilepticus.
Hippocampal neuronal loss plays an important role in epileptogenesis, and it is considered a trigger of repeated spontaneous recurrent seizures (SRS). The BDNF/TrkB signaling pathway regulates neuronal plasticity in the CNS, and promotes epileptogenesis. Previous studies have shown that Peroxisome proliferator-activated receptor gamma (PPARγ) agonists exert neuroprotective effects by inhibiting oxidative stress and inflammation in epilepsy. In the present study, the PPARγ agonist rosiglitazone inhibited increases in BDNF and TrkB after status epilepticus (SE), and also prevented hippocampal neuronal loss. More importantly, our study showed that rosiglitazone suppressed SRS. However, the effects of rosiglitazone were significantly reversed by cotreatment with K252a, an antagonist of TrkB. Additionally, rosiglitazone did not affect the development and severity of SE. Thus, our data provide evidence that rosiglitazone exerts neuroprotective and antiepileptic effects involve BDNF/TrkB signaling. Our study also offers new perspectives for the treatment of epilepsy.
Department of Neurology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China. Electronic address: sunhongxjt@yahoo.cn.
Sun
S
Hong
Yu
Y
Xin
Wu
W
HaiQin
Zhang
Z
GuiLian
Zhang
Z
Ru
Zhan
Z
ShuQin
Wang
W
HuQing
Yao
Y
Li
Bu
B
Ning
Li
L
YongNan
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004569:Electroencephalography; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects*; D047495:PPAR gamma / Q000819:agonists*; D010862:Pilocarpine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism*; D012008:Recurrence; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects*; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D045162:Thiazolidinediones / Q000494:pharmacology*
D000927:Anticonvulsants; D019208:Brain-Derived Neurotrophic Factor; D047495:PPAR gamma; D045162:Thiazolidinediones; D010862:Pilocarpine; D000077154:Rosiglitazone; D020813:Receptor, trkB
BDNF; Epilepsy; K252a; PPARγ; Rosiglitazone; Spontaneous recurrent seizures; TrkB