A study of autophagy flux abnormal block in atypical hippocampal sclerosis_Journal of Epilepsy

Authors：

XIONG Weixi , WU Mengqian , ZHANG Le , CHI Xiaosa , LI Jinmei ,  ZHOU Dong

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

Corresponding author：

ZHOU Dong, Email: zhoudong66@yahoo.de

Keywords：

Atypical hippocampal sclerosis; Autophagy; Temporal lobe epilepsy

DOI：

10.7507/2096-0247.20170058

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Objective The abnormal autophagy fluxis involved in the pathophysiological process of drug-resistance temporal lobe epilepsy (TLE).Hippocampal sclerosis (HS) is the main pathological type of drug-resistance TLE.Different subtypes of HS have various prognosis, etiology and pathophysiology.However, whether theabnormal block ofautophagy flux involved in this process has not been reported.This study proposed a preliminary comparison of autophagy fluxin typical and atypical HS to investigate the potential pathogenesis and drug-resistance mechanism of atypical HS. Methods Surgical excision of hippocampal and temporal lobe epilepsy foci were performed in 17 patients with drug-resistance TLE.Patients were grouped according to the HS classification issued by International League Against Epilepsy in 2013.The distribution and expression of LC3B, beclin-1 and P62 were detected by immunohistochemistry and Western blot in each group. Results LC3B, beclin-1 and P62 are mainly expressed in neuronal cytoplasm, which is consistent with previous reports.Taking β-actin as internal reference, we found that LC3B and Beclin-1, the downstream products of autophagy flux, have increased significantly (P < 0.01) in the atypical HS group compared to typical HS group.However, the autophagy flux substrate P62 has no difference between the groups.This result suggested that compared with the typical HS group, atypical HS group had autophagy substrate accumulation and autophagy flux abnormal block.Besides, we found that glyceraldehycle-3-phosphate dehydrogenase(GAPDH) was significantly different between the two groups (P=0.003). Conclusion There is abnormal phenomenon of autophagy flux in atypical HS, and GAPDH elevation may be involved in its mechanism, which might provide new targets and ideas for future treatment of atypical HS.

Citation： XIONG Weixi, WU Mengqian, ZHANG Le, CHI Xiaosa, LI Jinmei, ZHOU Dong. A study of autophagy flux abnormal block in atypical hippocampal sclerosis. Journal of Epilepsy, 2017, 3(5): 380-384. doi: 10.7507/2096-0247.20170058 Copy

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13.	Chang C, Su H, Zhang D, et al. AMPK-dependent phosphorylation of GAPDH triggers sirt1 activation and is necessary for autophagy upon glucose starvation.Mol Cell, 2015, 60(6): 930-940.

1. Semah F, Picot MC, Adam C, et al. Is the underlying cause of epilepsy a major prognostic factor for recurrence.Neurology, 1998, 51(5): 1256-1262.
2. Thom M.Review: Hippocampal sclerosis in epilepsy: a neuropathology review.Neuropathol Appl Neurobiol, 2014, 40(5): 520-543.
3. Blumcke I, Thom M, Aronica E, et al. International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: a Task Force report from the ILAE Commission on Diagnostic Methods.Epilepsia, 2013, 54(7): 1315-1329.
4. Blumcke I, Pauli E, Clusmann H, et al. A new clinico-pathological classification system for mesial temporal sclerosis.Actaneuropathol, 2007, 113(3): 235-244.
5. Yang Z, Klionsky DJ.Eaten alive: a history of macroautophagy.Nat Cell Biol, 2010, 12(9): 814-822.
6. Wu M, Liu X, Chi X, et al. Mitophagy in Refractory Temporal Lobe Epilepsy Patients with Hippocampal Sclerosis.Cell Mol Neurobiol, published online, 12 April 2017.
7. Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies.Epilepsia, 2010, 51(5): 1069-1077.
8. Klionsky DJ, Abdalla FC, Abeliovich H, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy, 2012, 8(4): 445-544.
9. Martinez-Vicente M.Neuronal Mitophagy in Neurodegenerative Diseases.Front Mol Neurosci, 2017, 10: 64.
10. Giorgi FS, Biagioni F, Lenzi P, et al. The role of autophagy in epileptogenesis and in epilepsy-induced neuronal alterations. J Neural Transm (Vienna), 2015, 122(6): 849-862.
11. Shacka JJ, Lu J, Xie ZL, et al. Kainic acid induces early and transient autophagic stress in mouse hippocampus.Neuroscilett, 2007, 414(1): 57-60.
12. Cao L, Xu J, Lin Y, et al. Autophagy is upregulated in rats with status epilepticus and partly inhibited by Vitamin E.Biochem Biophys Res Commun, 2009, 379(4): 949-953.
13. Chang C, Su H, Zhang D, et al. AMPK-dependent phosphorylation of GAPDH triggers sirt1 activation and is necessary for autophagy upon glucose starvation.Mol Cell, 2015, 60(6): 930-940.

Journal of Epilepsy

A study of autophagy flux abnormal block in atypical hippocampal sclerosis

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