Correlation study of mTOR pathway and pharmacoresistance of Sprague-Dawley rat epilepsy model kindled by coriaria lactone_Journal of Epilepsy

Authors：

 CHIXiaosa , HUANGcheng , WUMengqian ,  ZHOUDong

Department of Neurology, West China Hospital of Sichuan University, Chengdu 610041, China;

Corresponding author：

ZHOUDong, Email: zhoudong66@yahoo.de

Keywords：

mTOR; Refractory epilepsy; Coriaria lactone; Rats

DOI：

10.7507/2096-0247.20150037

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the association between mTOR pathway and pharmacoresistance of Sprague-Dawley rat epilepsy model kindled by coriaria lactone. Methods A kindling model of pharmacoresistant temporal lobe epilepsy was developed by injecting Sprague-Dawley (SD) rats with coriaria lactone (CL) (1.75 mg/kg, every 84 h). Normal SD rats were injected with normal sodium (NS) served as control group. Rats with five or more consecutive stage 5 seizures were included in kindled group. Immunohistochemistry was used to detect the levels of P-S6 in both groups. Results The expressions of P-S6 in CA1 and CA3 were significantly higher compared with control group, and were mainly in astrocytes (P < 0.001). In addition, the expression of P-S6 in DG area was significantly higher than that in control group, with more granular cell and neuron (P < 0.001). Conclusions The mTOR pathway may be correlated with the drug resistance of refractory lobe epilepsy kindled by coriaria lactone.

Citation： CHIXiaosa, HUANGcheng, WUMengqian, ZHOUDong. Correlation study of mTOR pathway and pharmacoresistance of Sprague-Dawley rat epilepsy model kindled by coriaria lactone. Journal of Epilepsy, 2015, 1(3): 225-228. doi: 10.7507/2096-0247.20150037 Copy

1.	Ngugi AK, Bottomley C, Kleinschmidt I, et al. Estimation of the burden of active and life-time epilepsy:a meta-analytic approach. Epilepsia, 2010, 51(5):883-890.
2.	Kwan P, Brodie MJ. Early identification of refractory epilepsy. The New England Journal of Medicine, 2000, 342(5):314-319.
3.	ZhaKwng C, An P, Zuo Z, et al. The transport of antiepileptic drugs by P-glycoprotein. Advanced Drug Delivery Reviews, 2012, 64(10):930-942.
4.	Lazarowski A, Czornyj L. Potential role of multidrug resistant proteins in refractory epilepsy and antiepileptic drugs interactions. Drug Metabolism and Drug Interactions, 2011, 26(1):21-26.
5.	Curatolo P, Jówiak S, Nabbout R, et al. Management of epilepsy associated with tuberous sclerosis complex (TSC):clinical recommendation. European Journal of Paediatric Neurology, 2012, 16(6):582-586.
6.	Sosunov AA, Wu X, McGovern RA, et al. The mTOR pathway is activated in glial cells in mesial temporal sclerosis. Epilepsia, 2012, 53(Suppl 1):78-86.
7.	Meng XF, Yu JT, Song JH, et al. Role of the mTOR signaling pathway in epilepsy. Journal of the Neurological Sciences, 2013, 332(1/2):4-15.
8.	Berdichevsky Y, Dryer AM, Saponjian Y, et al. PI3K-Akt signaling activates mTOR-mediated epileptogenesis in organotypic hippocampal culture model of post-Traumatic epilepsy. The Journal of Neuroscience, 2013, 33(21):9056-9067.
9.	Wang Y, Zhou D, Wang B, et al. A kindling model of pharmacoresistant temporal lobe epilepsy in Sprague-Dawley rats induced by Coriaria lactone and its possible mechanism. Epilepsia, 2003, 44(4):475-488.
10.	Racine RJ. Modification of seizure activity by electrical stimulation:II. Motor seizure. Electroencephalogr Clin Neurophysiol, 1972, 32(3):281-294.
11.	Heidi Munger Clary, Hyunmi Choi. Prognosis of Intractable Epilepsy:Is Long-Term Seizure Freedom Possible with Medical Management? Current Neurology and Neuroscience Reports, 2011, 11(4):409-417.
12.	Feliciano DM, Lin TV, Hartman NW, et al. A circuitry and biochemical basis for tuberous sclerosis symptoms:From epilepsy to neurocognitive deficits. International Journal of Developmental Neuroscience, 2013, 31(7):667-678.
13.	Russo E, Citraro R, Donato G, et al. mTOR inhibition modulates epileptogenesis, seizures and depressive behavior in a genetic rat model of absence epilepsy. Neuropharmacology, 2013, 6(9):25-36.
14.	Emilio Russo, Rita Citraro, Andrew Constanti, et al. The mTOR signaling pathway in the brain:focus on epilepsy and epileptogenesis. Molecular Neurobiology, 2012, 46(3):662-681.
15.	张立霞, 王赞, 邱吉庆, 等. mTOR信号通路在难治性癫痫中的作用机制.癫痫杂志, 2015, 1(1):17-21.
16.	Cho CH. Frontier of epilepsy research-mTOR signaling pathway. Experimental & Molecular Medicine, 2011, 43(5):231-274.
17.	Karin Boer, Dirk Troost, Wendy Timmermans, et al. PI3K-mTOR signaling and AMOG expression in epilepsy-associated glioneuronal tumors. Brain Pathology, 2010, 20(1):234-244.
18.	Robin CC Ryther, Michael Wong. Mammalian target of rapamycin (mTOR) inhibition:potential for antiseizure, antiepileptogenic, and epileptostatic therapy. Current Neurology and Neuroscience Reports, 2012, 12(4):410-418.
19.	Wong M. Mammalian target of rapamycin (mTOR) inhibition as a potential antiepileptogenic therapy:From tuberous sclerosis to common acquired epilepsies. Epilepsia, 2010, 51(1):27-36.
20.	Aldonza MB, Hong JY, Bae SY, et al. Suppression of MAPK signaling and reversal of mTOR-dependent MDR1-associated multidrug resistance by 21α-Methylmelianodiol in lung cancer cells. Plos One, 2015, 10(6):e0127841.
21.	David S Miller, Ronald E Cannon. Signaling pathways that regulate basal ABC transporter activity at the blood-brain barrier. Current Pharmaceutical Design, 2014, 20(10):1463-1471.

1. Ngugi AK, Bottomley C, Kleinschmidt I, et al. Estimation of the burden of active and life-time epilepsy:a meta-analytic approach. Epilepsia, 2010, 51(5):883-890.
2. Kwan P, Brodie MJ. Early identification of refractory epilepsy. The New England Journal of Medicine, 2000, 342(5):314-319.
3. ZhaKwng C, An P, Zuo Z, et al. The transport of antiepileptic drugs by P-glycoprotein. Advanced Drug Delivery Reviews, 2012, 64(10):930-942.
4. Lazarowski A, Czornyj L. Potential role of multidrug resistant proteins in refractory epilepsy and antiepileptic drugs interactions. Drug Metabolism and Drug Interactions, 2011, 26(1):21-26.
5. Curatolo P, Jówiak S, Nabbout R, et al. Management of epilepsy associated with tuberous sclerosis complex (TSC):clinical recommendation. European Journal of Paediatric Neurology, 2012, 16(6):582-586.
6. Sosunov AA, Wu X, McGovern RA, et al. The mTOR pathway is activated in glial cells in mesial temporal sclerosis. Epilepsia, 2012, 53(Suppl 1):78-86.
7. Meng XF, Yu JT, Song JH, et al. Role of the mTOR signaling pathway in epilepsy. Journal of the Neurological Sciences, 2013, 332(1/2):4-15.
8. Berdichevsky Y, Dryer AM, Saponjian Y, et al. PI3K-Akt signaling activates mTOR-mediated epileptogenesis in organotypic hippocampal culture model of post-Traumatic epilepsy. The Journal of Neuroscience, 2013, 33(21):9056-9067.
9. Wang Y, Zhou D, Wang B, et al. A kindling model of pharmacoresistant temporal lobe epilepsy in Sprague-Dawley rats induced by Coriaria lactone and its possible mechanism. Epilepsia, 2003, 44(4):475-488.
10. Racine RJ. Modification of seizure activity by electrical stimulation:II. Motor seizure. Electroencephalogr Clin Neurophysiol, 1972, 32(3):281-294.
11. Heidi Munger Clary, Hyunmi Choi. Prognosis of Intractable Epilepsy:Is Long-Term Seizure Freedom Possible with Medical Management? Current Neurology and Neuroscience Reports, 2011, 11(4):409-417.
12. Feliciano DM, Lin TV, Hartman NW, et al. A circuitry and biochemical basis for tuberous sclerosis symptoms:From epilepsy to neurocognitive deficits. International Journal of Developmental Neuroscience, 2013, 31(7):667-678.
13. Russo E, Citraro R, Donato G, et al. mTOR inhibition modulates epileptogenesis, seizures and depressive behavior in a genetic rat model of absence epilepsy. Neuropharmacology, 2013, 6(9):25-36.
14. Emilio Russo, Rita Citraro, Andrew Constanti, et al. The mTOR signaling pathway in the brain:focus on epilepsy and epileptogenesis. Molecular Neurobiology, 2012, 46(3):662-681.
15. 张立霞, 王赞, 邱吉庆, 等. mTOR信号通路在难治性癫痫中的作用机制.癫痫杂志, 2015, 1(1):17-21.
16. Cho CH. Frontier of epilepsy research-mTOR signaling pathway. Experimental & Molecular Medicine, 2011, 43(5):231-274.
17. Karin Boer, Dirk Troost, Wendy Timmermans, et al. PI3K-mTOR signaling and AMOG expression in epilepsy-associated glioneuronal tumors. Brain Pathology, 2010, 20(1):234-244.
18. Robin CC Ryther, Michael Wong. Mammalian target of rapamycin (mTOR) inhibition:potential for antiseizure, antiepileptogenic, and epileptostatic therapy. Current Neurology and Neuroscience Reports, 2012, 12(4):410-418.
19. Wong M. Mammalian target of rapamycin (mTOR) inhibition as a potential antiepileptogenic therapy:From tuberous sclerosis to common acquired epilepsies. Epilepsia, 2010, 51(1):27-36.
20. Aldonza MB, Hong JY, Bae SY, et al. Suppression of MAPK signaling and reversal of mTOR-dependent MDR1-associated multidrug resistance by 21α-Methylmelianodiol in lung cancer cells. Plos One, 2015, 10(6):e0127841.
21. David S Miller, Ronald E Cannon. Signaling pathways that regulate basal ABC transporter activity at the blood-brain barrier. Current Pharmaceutical Design, 2014, 20(10):1463-1471.

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Correlation study of mTOR pathway and pharmacoresistance of Sprague-Dawley rat epilepsy model kindled by coriaria lactone

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