Abstract OBJECTIVE: To observe the expression of dynamin-1 and phosphor-dynamin-1 in the hippocampus of children and rats with mesial temporal lobe epilepsy (MTLE) and to investigate the roles of dynamin-1 and phosphor-dynamin-1 in the development of MTLE. METHODS: Male Sprague-Dawley rats (aged 25 days) were randomly divided into acute control (AC), acute seizure (AS), latent control (LC), latent seizure (LS), chronic control (CC) and chronic spontaneous seizure (CS) groups. Lithium chloride-pilocarpine was used to induce a rat model of MTLE. The hippocampus samples of 5 children with a pathologically confirmed hippocampal sclerosis who received surgical operation were collected as a human model (HM) group, and the hippocampus samples of 4 dead children (without organic lesion of the hippocampus) were collected by autopsy as a human control (HC) group. The expression of dynamin-1 and phosphor-dynamin-1 in the hippocampus of children and rats with MTLE was measured by Western blot and immunohistochemistry. RESULTS: The Western blot showed that the expression of phosphor-dynamin-1 was significantly lower in the AS and CS groups than in the corresponding control groups (AC and CC groups) (P<0.05). The expression of phosphor-dynamin-1 was significantly lower in the HM group than in the HC group (P<0.05). There were no significant differences in the expression of dynamin-1 among the AS, LS and CS groups and between the HM and HC groups (P>0.05). The immunohistochemical results showed that phosphor-dynamin-1 was highly expressed in the cytoplasm of hippocampal neurons of AC, CC and HC groups, but its expression was significantly reduced in the AS, CS and HM groups (P<0.05). CONCLUSIONS: The expression of phosphor-dynamin-1, not dynamin-1, is downregulated in the hippocampus of children and rats with MTLE during seizures, which suggests that the phosphorylation/dephosphorylation of dynamin-1 may be involved in the development of MTLE.
ZHANG Ci-Liu,YIN Fei,YANG Zhi-Quan et al. Expression of dynamin-1 and phosphor-dynamin-1 in the hippocampus of children and rats with mesial temporal lobe epilepsy[J]. CJCP, 2013, 15(2): 133-137.
ZHANG Ci-Liu,YIN Fei,YANG Zhi-Quan et al. Expression of dynamin-1 and phosphor-dynamin-1 in the hippocampus of children and rats with mesial temporal lobe epilepsy[J]. CJCP, 2013, 15(2): 133-137.
[13]Ferguson SM, Brasnjo G, Hayashi M, W-lfel M, Collesi C, Giovedi S, et al. A selective activity-dependent requirement for dynamin 1 in synaptic vesicle endocytosis[J]. Science, 2007, 316(5824): 570-574.
[1]Muramatsu R,Ikegaya Y,Matsuki N, Koyama R. Early-life status epilepticus induces ectopic granule cells in adult mice dentate gyrus[J]. Exp Neurol, 2008, 211(2): 503-510.
[2]Wahab A, Albus K, Heinemann U. Age and region specific effects of anticonvulsants and bumetanide on 4-aminopyridine induced seizure like events in hippocampal-entorhinal cortex slices[J]. Epilepsia, 2011, 52(1): 94-103.
[3]Schmid EM, McMahon HT. Integrating molecular and network biology to decode endocytosis[J]. Nature, 2007, 448(7156): 883-888.
[4]Ferguson SM, De Camilli P. Dynamin, a membrane-remodelling GTPase[J]. Nat Rev Mol Cell Biol, 2012, 13(2): 75-88.
[5]Clayton EL, Anggono V, Smillie KJ, Chau N, Robinson PJ, Cousin MA. The phospho-dependent dynamin-syndapin interaction triggers activity-dependent bulk endocytosis of synaptic vesicles[J]. J Neurosci, 2009, 29(24): 7706-7717.
[7]Boumil RM, Letts VA, Roberts MC, Lenz C, Mahaffey CL, Zhang ZW, et al. A missense mutation in a highly conserved alternate exon of dynamin-1 causes epilepsy in fitful mice[J]. PLoS Genet, 2010, 6(8): e1001046.
[8]Wu L, Peng J, Wei C, Liu G, Wang G, Li K, et al. Characterization, using comparative proteomics, of differentially expressed proteins in the hippocampus of the mesial temporal lobe of epileptic rats following treatment with valproate[J]. Amino Acids, 2011, 40(1): 221-238.
[9]Graham ME, Anggono V. The in vivo phosphorylation sites of rat brain dynamin I[J]. J Biol Chem, 2007, 282(20): 14695-14707.
[10]Proper EA, Jansen GH, van Veelen CW, van Rijen PC, Gispen WH, de Graan PN. A grading system for hippocampal sclerosis based on the degree of hippocampal mossy fiber sprouting[J]. Acta Neuropathol, 2001, 101(4): 405-409.
[12]Smillie KJ, Cousin MA. Dynamin I phosphorylation and the control of synaptic vesicle endocytosis[J]. Biochem Soc Symp, 2005, (72): 87-97.
[13]Ferguson SM, Brasnjo G, Hayashi M, W-lfel M, Collesi C, Giovedi S, et al. A selective activity-dependent requirement for dynamin 1 in synaptic vesicle endocytosis[J]. Science, 2007, 316(5824): 570-574.