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Smad anchor for receptor activation contributes to seizures in temporal lobe epilepsy
Author(s) -
Yu Weihua,
Du Yingshi,
Zou Yan,
Wang Xuefeng,
Stephani Ulrich,
Lü Yang
Publication year - 2017
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.21957
Subject(s) - epileptogenesis , epilepsy , smad , status epilepticus , pilocarpine , hippocampus , transforming growth factor , neuroscience , gene knockdown , receptor , signal transduction , medicine , endocrinology , microbiology and biotechnology , biology , apoptosis , biochemistry
Purpose Smad anchor for receptor activation (SARA) is an important regulator of transforming growth factor β (TGF‐β) signaling by recruiting Smad2/3 to TGF‐β receptors. Although TGF‐β signaling is critically involved in epileptogenesis, whether SARA activation is sufficient to facilitate TGF‐β pathway to regulate epilepsy remains unknown. Methods The expression of SARA and downstream Phospho‐Smad3 (p‐Smad3) was examined in rats with pilocarpine induced epilepsy. Additionally, knockdown of SARA was performed via recombinant lentiviral vector in the pilocarpine‐induced rats. Results Here we show that expressions of SARA and p‐Smad3 are increased in the hippocampus as rats subjected to pilocarpine‐induced status epilepticus (SE). Both SARA and p‐Smad3 are also upregulated in the temporal cortex of epileptic rats. Furthermore, SARA mRNA levels reach peak as early as 6 hr following SE onset and remain elevated in the chronic phase. Transfection of recombinant lentiviral shRNA targeting SARA knocks down SARA expression, attenuates TGF‐β/p‐Smad3 signaling in the hippocampus, and postpones the SE onset. Conclusion Our results demonstrate that SARA/Smad3 pathway contributes to mechanism of seizure and SARA in TGF‐β signaling may be a potential therapeutic target for epilepsy.