Overexpression of N-WASP in the brain of human epilepsy.
Neuronal circuit remodeling is the most critical pathological characteristic closely associated with the initiation and maintenance of epilepsy; however, the exact mechanisms of neuronal remodeling need further elucidation. Neuronal Wiskott-Aldrich syndrome protein (N-WASP) is a key regulator of the actin cytoskeleton that causes actin polymerization and thus neurite extension. Our previous research demonstrated that the upstream regulator of N-WASP, cell division cycle 42 GTP-binding protein (Cdc42), is significantly upregulated in the brains of patients with intractable epilepsy (IE). In addition, cDNA microarray analysis has shown that gene expression of N-WASP is notably enhanced in the epileptic brain, suggesting a possible role for N-WASP in epileptogenesis. Here, we investigated the expression of N-WASP and its downstream effector, actin-related protein 2/3 (Arp2/3), at the protein level in the temporal lobe of IE patient brains to explore its possible role in the genesis of IE. Forty surgical samples from brains of patients with IE and 20 control brain tissues were obtained for this study. The expression of N-WASP in the anterior temporal neocortex was detected using immunohistochemistry, immunofluorescence and western blotting; Arp2/3 expression was detected by western blotting. Compared with controls, N-WASP expression in brains of IE patients was significantly higher; similarly, Arp2/3 level was markedly increased in the IE patient group. These results suggest that increased expression of N-WASP in the human brain may be associated with human IE.
Xiao
Fei
F
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 You Yi Road, Chongqing 400016, China.
Wang
Xue-feng
XF
Li
Jin-mei
JM
Xi
Zhi-qin
ZQ
Lu
Yang
Y
Wang
Liang
L
Zeng
Yan
Y
Guan
Li-feng
LF
Yuan
Jie
J
D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D004827:Epilepsy / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012016:Reference Values; D013702:Temporal Lobe / Q000378:metabolism*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism*; D055815:Young Adult
D051376:Actin-Related Protein 2-3 Complex; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal