Identification of novel electroconvulsive shock-induced and activity-dependent genes in the rat brain Woong Sun a,1 , Kun Woo Park b,1 , Jeehyung Choe a , Im Joo Rhyu a , Il Hwan Kim a , Soon Kwon Park a , Byungil Choi a , Sang-Hyun Choi c , Sun Hwa Park a , Hyun Kim a, * a Division of Brain, Department of Anatomy, Korea 21 Biomedical Science, Korea University College of Medicine, 126-1, 5-Ka, Anam-Dong, Seongbuk-Gu, Seoul 136-705, Republic of Korea b Department of Neurology, Korea University College of Medicine, 126-1, 5-Ka, Anam-Dong, Seongbuk-Gu, Seoul 136-705, Republic of Korea c Department of Pharmacology, Korea University College of Medicine, 126-1, 5-Ka, Anam-Dong, Seongbuk-Gu, Seoul 136-705, Republic of Korea Received 6 December 2004 Available online 20 December 2004 Abstract Electroconvulsive shock (ECS) has been used as an effective treatment for patients suffering from major depression disorders and schizophrenia. However, the exact mechanisms underlying the action of ECS are poorly understood. Using high-density oligonu- cleotide microarrays, we identified 60 ECS-induced genes whose gene products are involved in the neuronal signaling, neuritogenesis and tissue remodeling. In situ hybridization and depolarization-dependent expression assay were performed to characterize 4 genes (lysyl oxidase, Ab1-046, SOX11, and T-type calcium channel 1G subunit) which have not yet been reported to be induced by ECS. Interestingly, the induction of these genes was observed mainly in the dentate gyrus of hippocampal formation and piriform cortex, where ECS-induced neural activation is highlighted, and depolarization of cultured cortical neurons also induced the expression of these genes. Taken together, our results suggest that therapeutic actions of ECS may be manifested by the activity-dependent induc- tion of genes related to the plastic changes of the brain such as neuronal signaling neuritogenesis, and tissue remodeling. Ó 2004 Elsevier Inc. All rights reserved. Keywords: Electroconvulsive shock; Microarray; Neural activity; Tissue remodeling Electroconvulsive shock (ECS) is effective therapeutic tool for depressive patients who do not respond to chemical antidepressants. Although the mechanism(s) underlying the therapeutic activity of ECS treatment is unclear, there are several reports proposing possible involvement of glutamate receptors [1], neurotrophic factors [2,3], immediate early transcription factors [4– 6], and intracellular second messenger signaling-related molecules [6,7]. The alterations of these genes might give rise to the subsequent changes in the neurotransmission, tissue remodeling, and neurogenesis. Multiple changes of the genes involved in these diverse biochemical events suggest that the therapeutic effect of ECS may be medi- tated by the changes of multiple biochemical pathways, but not by any of a single gene product. In this respect, exploration of the novel biochemical pathways or genes whose expressions are regulated by ECS may be impor- tant to understand the mechanism of ECS. Advent of microarray technology allows us to assess the changes in the gene expression profiles on a genome- wide scale. Recently, this advantage has been success- fully applied to the ECS study and the involvement of neurotrophic, angiogenic, and neuritogenic processes is proposed [6,7]. Using high-density Affymetrix oligonu- cleotide chip, here we identified ECS-induced genes, 0006-291X/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.bbrc.2004.12.050 * Corresponding author. Fax: +82 2 929 5696. E-mail address: kimhyun@korea.ac.kr (H. Kim). 1 These authors equally contributed to this study and are co-first authors. www.elsevier.com/locate/ybbrc Biochemical and Biophysical Research Communications 327 (2005) 848–856 BBRC