Electroconvulsive seizure-induced gene expression profile of the hippocampus dentate gyrus granule cell layer.
Electroconvulsive shock (ECS) is the most effective treatment for depression, but the mechanism underlying the therapeutic action of this treatment is still unknown. To better understand the molecular changes that may be necessary for the clinical effectiveness of ECS we have combined the technologies of gene expression profiling using cDNA microarrays with T7-based RNA amplification and laser microdissection to identify regulated genes in the dentate gyrus granule cell layer of the hippocampus. We have identified genes previously reported to be up-regulated following ECS, including brain-derived neurotrophic factor, neuropeptide Y, and thyrotrophin releasing hormone, as well as several novel genes. Notably, we have identified additional genes that are known to be involved in neuroprotection, such as growth arrest DNA damage inducible beta (Gadd45beta), and the excitatory amino acid transporter-1 (EAAC1/Slc1A1). In addition, via in situ hybridization we show that EAAC1 is specifically up-regulated in the dentate gyrus, but not in other hippocampal subfields. This study demonstrates the utility of microarray analysis of microdissected subregions of limbic brain regions and identifies novel ECS-regulated genes.
Ploski
Jonathan E
JE
Laboratory of Molecular Psychiatry, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06508, USA.
Newton
Samuel S
SS
Duman
Ronald S
RS
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism*; D003866:Depressive Disorder / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D004195:Disease Models, Animal; D004597:Electroshock; D050580:Excitatory Amino Acid Transporter 3 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D020869:Gene Expression Profiling / Q000379:methods; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009478:Neuropeptide Y / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013973:Thyrotropin-Releasing Hormone / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D000097642:GADD45 Proteins
D000943:Antigens, Differentiation; D019208:Brain-Derived Neurotrophic Factor; D050580:Excitatory Amino Acid Transporter 3; D018698:Glutamic Acid; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D012333:RNA, Messenger; D013973:Thyrotropin-Releasing Hormone; C508094:Gadd45b protein, rat; D000097642:GADD45 Proteins; C493398:Slc1a1 protein, rat