title: Proteomic analysis on infantile spasm and prenatal stress.
abstract: Infantile spasms (IS) are an age-dependent epileptic encephalopathy with severe cognitive dysfunction. Prenatal stress (PS) has been reported to increase the risk for IS through clinical and animal studies. We aim to investigate the mechanism of brain damage caused by IS and the effect of PS. Animals were divided into 4 groups: PS-spasm model, PS-saline control, NS-spasm model, and saline control. N-methyl-d-aspartate (NMDA) was used to induce spasm and swimming in cold water was used to induce PS. A proteomics-based approach was used to compare the NS-spasm model vs. saline control, and PS-spasm model vs. NS-spasm model. Gel image analysis was followed by mass spectrometric protein identification and bioinformatics analysis. We observed an increased spasm frequency (t=8.65, P<0.001), and a shorter latency period (t=3.96, P<0.001) in the PS-spasm model vs. the NS-spasm model. In the NS-spasm model vs. saline control, the main differentially expressed proteins were CFL1, PKM2, PRPS2, DLAT, CKB, DPYSL3, and SNAP25. In the PS-spasm model vs. NS-spasm model, MDH1 and YWHAZ were differentially expressed. YWHAZ was directly connected with CFL1 in protein networks. YWHAZ and CFL1 were further validated by Western blot analysis. The biological function of differentially expressed proteins indicates the pathogenesis of IS maybe relevant to energy metabolism, brain development, and neural remodeling. PS aggravated seizures in the NMDA-induced spasm model, YWHAZ, and CFL1 may be involved.
authors.affiliation: Department of Pediatrics, General Hospital of Chinese People's Liberation Army, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, General Hospital of Chinese People's Liberation Army, Beijing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, General Hospital of Chinese People's Liberation Army, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, General Hospital of Chinese People's Liberation Army, Beijing, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, General Hospital of Chinese People's Liberation Army, Beijing, China.
authors.forename: Ai-Jia
authors.initials: AJ
authors.lastname: Shang
authors.affiliation: Department of Pediatrics, General Hospital of Chinese People's Liberation Army, Beijing, China. Electronic address: zouliping21@hotmail.com.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Zou
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D051338:Cofilin 1 / Q000378:metabolism*; D019295:Computational Biology; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D018832:Molecular Chaperones / Q000378:metabolism*; D016202:N-Methylaspartate / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism*; D060066:Protein Interaction Maps; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D013036:Spasms, Infantile / Q000139:chemically induced / Q000378:metabolism*; D013315:Stress, Psychological / Q000209:etiology / Q000378:metabolism*; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D048948:14-3-3 Proteins; C495812:Cfl1 protein, rat; D051338:Cofilin 1; D018690:Excitatory Amino Acid Agonists; D018832:Molecular Chaperones; C490391:Ywhaz protein, rat; D016202:N-Methylaspartate
keywords: Infantile spasms; Prenatal stress; Proteomic; YWHAZ