Abstract
Background: Fangjing decoction is a Traditional Chinese Medicine that exhibits anticonvulsive effects in treating febrile seizures (FS). Its action mechanism and the regulation on Akt/mammalian target of rapamycin (mTOR) pathway were revealed in the present study.Methods: FS model was established in Sprague–Dawley rats with or without Fangjing decoction treatment. On day 5, following initiation of drug treatment, seizures were monitored. Hippocampal neuron apoptosis was assessed using terminal dUTP nick end-labeling method. The levels of Bax, protein kinase B (Akt), phospho-Akt (p-Akt), mTOR, and p-mTOR proteins were analyzed using Western blotting. The content of hippocampal γ-aminobutyric acid (GABA) was measured by using ELISA assay.Results: Compared with the control group (n=8), Fangjing decoction effectively shortened escape latency and duration of FS and decreased the frequency of FS in rats (n=8). Concomitantly, the apoptosis of hippocampal neurons, as well as Bax protein levels were also decreased in FS rats which were treated with Fangjing decoction. In addition, the Akt/mTOR signaling was found to be activated in rat hippocampus following FS, as evidenced by increased p-Akt and p-mTOR, while Fangjing decoction could inhibit the activation of Akt/mTOR signaling. Furthermore, the low GABA content in rat hippocampus following FS was significantly elevated by Fangjing decoction treatment. More importantly, SC79, a specific activator for Akt, apparently attenuated the protective effects of Fangjing decoction on FS rats.Conclusion: These results suggest that Fangjing decoction protects the hippocampal neurons from apoptosis by inactivating Akt/mTOR pathway, which may contribute to mitigating FS-induced brain injury.
Highlights
Febrile seizures (FS) are the most common type of convulsive events affecting up to 2–5% in infants as well as young children
Consistent studies exist with regard to the increased risk for developing brain injury by prolonged or recurrent febrile seizures (FS), leading to hippocampus and cortex neuron apoptosis, which in turn can result in cognitive dysfunctions
Fangjing decoction suppressed hippocampal neuron apoptosis in FS rats We further explored the biological functions of Fangjing decoction in hippocampal neuron apoptosis
Summary
Febrile seizures (FS) are the most common type of convulsive events affecting up to 2–5% in infants as well as young children. Consistent studies exist with regard to the increased risk for developing brain injury by prolonged or recurrent FS, leading to hippocampus and cortex neuron apoptosis, which in turn can result in cognitive dysfunctions. The Akt/mTOR signaling pathway has been reported to c 2018 The Author(s). The apoptosis of hippocampal neurons, as well as Bax protein levels were decreased in FS rats which were treated with Fangjing decoction. The low GABA content in rat hippocampus following FS was significantly elevated by Fangjing decoction treatment. Conclusion: These results suggest that Fangjing decoction protects the hippocampal neurons from apoptosis by inactivating Akt/mTOR pathway, which may contribute to mitigating FS-induced brain injury
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