Aberrant expression of cytoskeleton proteins in hippocampus from patients with mesial temporal lobe epilepsy

Abstract

Mesial temporal lobe epilepsy (MTLE), the most common form of epilepsy, is characterised by cytoarchitectural abnormalities including neuronal cell loss and reactive gliosis in hippocampus. Determination of aberrant cytoskeleton protein expression by proteomics techniques may help to understand pathomechanism that is still elusive. We searched for differential expression of hippocampal proteins by an analytical method based on two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry unambiguously identifying 77 proteins analysed in eight control and eight MTLE hippocampi. Proteins were quantified and we observed 18 proteins that were altered in MTLE. Cytoskeleton proteins tubulin alpha-1 chain, beta-tubulin, profilin II, neuronal tropomodulin were significantly reduced and one actin spot was missing, whereas ezrin and vinculin were significantly increased in MTLE. Proteins of several classes as e.g. antioxidant proteins (peroxiredoxins 3 and 6), chaperons (T-complex protein 1-alpha, stress-induced-phosphoprotein 1), signaling protein MAP kinase kinase 1, synaptosomal proteins (synaptotagmin I, alpha-synuclein), NAD-dependent deacetylase sirtuin-2 and 26S protease regulatory subunit 7 protein, neuronal-specific septin 3 were altered in MTLE. Taken together, the findings may represent or lead to cytoskeletal impairment; aberrant antioxidant proteins, chaperons, MAP kinase kinase 1 and NAD-dependent deacetylase sirtuin-2 may have been involved in pathogenetic mechanisms and altered synaptosomal protein expression possibly reflects synaptic impairment in MTLE.

High-Throughput LC–MS/MS Proteomic Analysis of a Mouse Model of Mesiotemporal Lobe Epilepsy Predicts Microglial Activation Underlying Disease Development

“…When proteomic analysis using two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry was performed in human MTLE hippocampi, differential 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 28 expression of Ezrin (up, 5.3 fold) and Map2k4 (down, 0.56 fold) was suggested, in agreement with our findings 94 .…”

Proteomic analysis of striatal neuronal cell cultures after morphine administration

“…Stressinduced phosphoprotein 1 is a component of a dynamic heterocomplex chaperoning machine involved in maturation of different molecules [59]. This protein was also upregulated in the hippocampus from patients with mesial temporal lobe epilepsy, which may suggest a role of this protein in neurological disorders [60].…”

Generalization of seizures parallels the formation of “dark” neurons in the hippocampus and pontine reticular formation after focal–cortical application of 4-aminopyridine (4-AP) in the rat

“…During electrographic seizures and sustained depolarization, the elevated intracellular Ca ++ can result in both pathological and protective changes in the cellular protein composition of neurons or glial cells. These changes in the cellular proteom are under intense investigation in epilepsy research (Eun et al, 2004;Greene et al, 2007;Jiang et al, 2007;Junker et al, 2005;Ryu et al, 2007;Yang et al, 2006). Some of the available results emphasize the role of cytoskeletal impairment and cytoskeletal rearrangement in epilepsy (Greene et al, 2007;Ryu et al, 2007;Yang et al, 2006).…”