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The antiepileptic effect of Gastrodiae Rhizoma through modulating overexpression of mTOR and attenuating astrogliosis in pilocarpine mice model

OBJECTIVE: To investigate the effect of water extract of Gastrodiae Rhizoma (GR) on the development of acquired temporal lobe epilepsy (TLE) and on regulating the expression of the mammalian target of rapamycin (mTOR) and semaphorin 3F (SEMA3F). METHODS: A pilocarpine‐induced status epilepticus (SE)...

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Autores principales: Yip, Ka Lai, Koon, Chi Man, Chen, Zi Yi, Chook, Ping, Leung, Ping Chung, Schachter, Steven, Leung, Wai Hong, Mok, Chung Tong, Leung, Howan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049815/
https://www.ncbi.nlm.nih.gov/pubmed/32140643
http://dx.doi.org/10.1002/epi4.12372
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author Yip, Ka Lai
Koon, Chi Man
Chen, Zi Yi
Chook, Ping
Leung, Ping Chung
Schachter, Steven
Leung, Wai Hong
Mok, Chung Tong
Leung, Howan
author_facet Yip, Ka Lai
Koon, Chi Man
Chen, Zi Yi
Chook, Ping
Leung, Ping Chung
Schachter, Steven
Leung, Wai Hong
Mok, Chung Tong
Leung, Howan
author_sort Yip, Ka Lai
collection PubMed
description OBJECTIVE: To investigate the effect of water extract of Gastrodiae Rhizoma (GR) on the development of acquired temporal lobe epilepsy (TLE) and on regulating the expression of the mammalian target of rapamycin (mTOR) and semaphorin 3F (SEMA3F). METHODS: A pilocarpine‐induced status epilepticus (SE) model was adopted to precipitate injury in the limbic systems. GR and carbamazepine (CBZ) treatments were given to mice for 14 days prior to SE induction to demonstrate the antiepileptic effects and continued for 5 more days to illustrate the effects on histologic studies. RESULTS: Our results consolidated that GR treatment (92.1 minutes) could delay the SE onset in comparison with the control group (61.5 minutes, P = .041). Fewer mice had reached SE with GR treatment (41.7%) when compared with the control group (83.3%, P = .044). GR treatment (2.1 hours/mouse) could suppress the number of acute seizures in post‐SE survival mice when compared with the control group (4.5 hours/mouse, P < .001). The effects of GR treatment were elucidated with the mechanism of actions. GR treatment reduced the overexpression of mTOR (0.27 vs 0.67 AU/mg protein, P = .047). GR treatment increased the underexpression of SEMA3F (0.51 vs 0.16 µg/mg protein, P = .034). In the histochemical study of microtubule‐associated protein 2 (MAP2) staining, our results showed that GR prevented neuronal loss in the GR treatment group (64.8% positively stained pixel area) as compared with the control group (59%, P = .014) in the hippocampus. In glial fibrillary acidic protein (GFAP) staining, the severity of astrogliosis was mitigated by the GR treatment (4.1% positively stained pixel area) when compared to the control group (5.6%, P = .047) in the hippocampus. SIGNIFICANCE: These results provide preclinical evidence to support the use of GR, which could suppress acute seizures and relieve pathological changes in pilocarpine‐induced TLE mice. We demonstrated that the antiepileptic effects of GR could be accompanied by mTOR reduction and astrogliosis attenuation.
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spelling pubmed-70498152020-03-05 The antiepileptic effect of Gastrodiae Rhizoma through modulating overexpression of mTOR and attenuating astrogliosis in pilocarpine mice model Yip, Ka Lai Koon, Chi Man Chen, Zi Yi Chook, Ping Leung, Ping Chung Schachter, Steven Leung, Wai Hong Mok, Chung Tong Leung, Howan Epilepsia Open Full‐length Original Research OBJECTIVE: To investigate the effect of water extract of Gastrodiae Rhizoma (GR) on the development of acquired temporal lobe epilepsy (TLE) and on regulating the expression of the mammalian target of rapamycin (mTOR) and semaphorin 3F (SEMA3F). METHODS: A pilocarpine‐induced status epilepticus (SE) model was adopted to precipitate injury in the limbic systems. GR and carbamazepine (CBZ) treatments were given to mice for 14 days prior to SE induction to demonstrate the antiepileptic effects and continued for 5 more days to illustrate the effects on histologic studies. RESULTS: Our results consolidated that GR treatment (92.1 minutes) could delay the SE onset in comparison with the control group (61.5 minutes, P = .041). Fewer mice had reached SE with GR treatment (41.7%) when compared with the control group (83.3%, P = .044). GR treatment (2.1 hours/mouse) could suppress the number of acute seizures in post‐SE survival mice when compared with the control group (4.5 hours/mouse, P < .001). The effects of GR treatment were elucidated with the mechanism of actions. GR treatment reduced the overexpression of mTOR (0.27 vs 0.67 AU/mg protein, P = .047). GR treatment increased the underexpression of SEMA3F (0.51 vs 0.16 µg/mg protein, P = .034). In the histochemical study of microtubule‐associated protein 2 (MAP2) staining, our results showed that GR prevented neuronal loss in the GR treatment group (64.8% positively stained pixel area) as compared with the control group (59%, P = .014) in the hippocampus. In glial fibrillary acidic protein (GFAP) staining, the severity of astrogliosis was mitigated by the GR treatment (4.1% positively stained pixel area) when compared to the control group (5.6%, P = .047) in the hippocampus. SIGNIFICANCE: These results provide preclinical evidence to support the use of GR, which could suppress acute seizures and relieve pathological changes in pilocarpine‐induced TLE mice. We demonstrated that the antiepileptic effects of GR could be accompanied by mTOR reduction and astrogliosis attenuation. John Wiley and Sons Inc. 2019-12-13 /pmc/articles/PMC7049815/ /pubmed/32140643 http://dx.doi.org/10.1002/epi4.12372 Text en © 2019 The Authors. Epilepsia Open published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full‐length Original Research
Yip, Ka Lai
Koon, Chi Man
Chen, Zi Yi
Chook, Ping
Leung, Ping Chung
Schachter, Steven
Leung, Wai Hong
Mok, Chung Tong
Leung, Howan
The antiepileptic effect of Gastrodiae Rhizoma through modulating overexpression of mTOR and attenuating astrogliosis in pilocarpine mice model
title The antiepileptic effect of Gastrodiae Rhizoma through modulating overexpression of mTOR and attenuating astrogliosis in pilocarpine mice model
title_full The antiepileptic effect of Gastrodiae Rhizoma through modulating overexpression of mTOR and attenuating astrogliosis in pilocarpine mice model
title_fullStr The antiepileptic effect of Gastrodiae Rhizoma through modulating overexpression of mTOR and attenuating astrogliosis in pilocarpine mice model
title_full_unstemmed The antiepileptic effect of Gastrodiae Rhizoma through modulating overexpression of mTOR and attenuating astrogliosis in pilocarpine mice model
title_short The antiepileptic effect of Gastrodiae Rhizoma through modulating overexpression of mTOR and attenuating astrogliosis in pilocarpine mice model
title_sort antiepileptic effect of gastrodiae rhizoma through modulating overexpression of mtor and attenuating astrogliosis in pilocarpine mice model
topic Full‐length Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049815/
https://www.ncbi.nlm.nih.gov/pubmed/32140643
http://dx.doi.org/10.1002/epi4.12372
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