Chongyang Tang1, Yunhe Gu2, Haiyang Wang3, Hongmei Wu4, Yu Wang5, Yao Meng6, Zhibin Han7, Yifei Gu8, Wei Ma9, Zhenfeng Jiang10, Yuanyuan Song11, Meng Na12, Dunyue Lu13, Zhiguo Lin14. 1. Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China. Electronic address: drtangchongyang@hotmail.com. 2. Department of Pathology, The First Affiliated Hospital, Harbin Medical University, Harbin, China. Electronic address: 263251535@qq.com. 3. Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China. Electronic address: drwanghaiyang@hotmail.com. 4. Department of Pathology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China. Electronic address: 18249085631@163.com. 5. Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China. Electronic address: 727814355@qq.com. 6. Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China. Electronic address: 979239770@qq.com. 7. Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China. Electronic address: 646580714@qq.com. 8. Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China. Electronic address: 825393826@qq.com. 9. Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China. Electronic address: 48708200@qq.com. 10. Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China. Electronic address: 404461054@qq.com. 11. Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China. Electronic address: 304492619@qq.com. 12. Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China. Electronic address: nameng2001@hotmail.com. 13. Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China. Electronic address: dunyuelu@gmail.com. 14. Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China. Electronic address: zhiguolin@outlook.com.
Abstract
OBJECTIVE: Studies have shown that microRNAs play a role in the development of epilepsy by regulating downstream target messenger (m)RNA. The present study aims to determine the changes associated with microRNA-21-5p (miR-21-5p) during epileptogenesis in a kainic acid rat model, and to assess whether the PTEN-mTOR pathway is a target of miR-21-5p. METHOD: Reverse transcription polymerase chain reaction (RT-PCR) was used to examine the quantitative expressions of miR-21-5p and PTEN, and Western blotting was used to test the activity of mTOR in the acute, latent, and chronic stages of epileptogenesis. The antagomir of miR-21-5p was injected into the intracerebroventricular space using a microsyringe. Neuronal death and epilepsy discharge were assessed by Nissl staining and electroencephalography (EEG), respectively. The Morris water maze (MWM) was used to assess the cognitive impairment in rats after status epilepticus (SE). RESULTS: Both miR-21-5p and mTOR were upregulated and PTEN was downregulated in rats during acute, latent, and chronic stages of epileptogenesis when compared with those of the control. After using antagomir miR-21-5p in vivo, miR-21-5p and mTOR decreased and the expression of PTEN increased compared with that in the SE model. The silencing of miR-21-5p diminished the number of abnormal spikes on EEG and decreased the number of neuron deletions on Nissl staining. The cognitive and memory impairment caused by epilepsy could also be improved after miR-21-5p knockdown in vivo. CONCLUSION: The results of the present study demonstrate that PTEN-mTOR is the target of miR-21-5p in a kainic acid model of epilepsy. The knockout of miR-21-5p decreases the neuronal damage in stages of epileptogenesis. The miR-21-5p/PTEN/mTOR axis may be a potential target for preventing and treating seizures and epileptic damage.
OBJECTIVE: Studies have shown that microRNAs play a role in the development of epilepsy by regulating downstream target messenger (m)RNA. The present study aims to determine the changes associated with microRNA-21-5p (miR-21-5p) during epileptogenesis in a kainic acidrat model, and to assess whether the PTEN-mTOR pathway is a target of miR-21-5p. METHOD: Reverse transcription polymerase chain reaction (RT-PCR) was used to examine the quantitative expressions of miR-21-5p and PTEN, and Western blotting was used to test the activity of mTOR in the acute, latent, and chronic stages of epileptogenesis. The antagomir of miR-21-5p was injected into the intracerebroventricular space using a microsyringe. Neuronal death and epilepsy discharge were assessed by Nissl staining and electroencephalography (EEG), respectively. The Morris water maze (MWM) was used to assess the cognitive impairment in rats after status epilepticus (SE). RESULTS: Both miR-21-5p and mTOR were upregulated and PTEN was downregulated in rats during acute, latent, and chronic stages of epileptogenesis when compared with those of the control. After using antagomir miR-21-5p in vivo, miR-21-5p and mTOR decreased and the expression of PTEN increased compared with that in the SE model. The silencing of miR-21-5p diminished the number of abnormal spikes on EEG and decreased the number of neuron deletions on Nissl staining. The cognitive and memory impairment caused by epilepsy could also be improved after miR-21-5p knockdown in vivo. CONCLUSION: The results of the present study demonstrate that PTEN-mTOR is the target of miR-21-5p in a kainic acid model of epilepsy. The knockout of miR-21-5pdecreases the neuronal damage in stages of epileptogenesis. The miR-21-5p/PTEN/mTOR axis may be a potential target for preventing and treating seizures and epileptic damage.
Authors: Morten T Venø; Cristina R Reschke; Gareth Morris; Niamh M C Connolly; Junyi Su; Yan Yan; Tobias Engel; Eva M Jimenez-Mateos; Lea M Harder; Dennis Pultz; Stefan J Haunsberger; Ajay Pal; Janosch P Heller; Aoife Campbell; Elena Langa; Gary P Brennan; Karen Conboy; Amy Richardson; Braxton A Norwood; Lara S Costard; Valentin Neubert; Federico Del Gallo; Beatrice Salvetti; Vamshidhar R Vangoor; Amaya Sanz-Rodriguez; Juha Muilu; Paolo F Fabene; R Jeroen Pasterkamp; Jochen H M Prehn; Stephanie Schorge; Jens S Andersen; Felix Rosenow; Sebastian Bauer; Jørgen Kjems; David C Henshall Journal: Proc Natl Acad Sci U S A Date: 2020-06-24 Impact factor: 11.205