Identification of activity-induced Egr3-dependent genes reveals genes associated with DNA damage response and schizophrenia.

Bioinformatics and network studies have identified the immediate early gene transcription factor early growth response 3 (EGR3) as a master regulator of genes differentially expressed in the brains of patients with neuropsychiatric illnesses ranging from schizophrenia and bipolar disorder to Alzheimer's disease. However, few studies have identified and validated Egr3-dependent genes in the mammalian brain. We have previously shown that Egr3 is required for stress-responsive behavior, memory, and hippocampal long-term depression in mice. To identify Egr3-dependent genes that may regulate these processes, we conducted an expression microarray on hippocampi from wildtype (WT) and Egr3-/- mice following electroconvulsive seizure (ECS), a stimulus that induces maximal expression of immediate early genes including Egr3. We identified 69 genes that were differentially expressed between WT and Egr3-/- mice one hour following ECS. Bioinformatic analyses showed that many of these are altered in, or associated with, schizophrenia, including Mef2c and Calb2. Enrichr pathway analysis revealed the GADD45 (growth arrest and DNA-damage-inducible) family (Gadd45b, Gadd45g) as a leading group of differentially expressed genes. Together with differentially expressed genes in the AP-1 transcription factor family genes (Fos, Fosb), and the centromere organization protein Cenpa, these results revealed that Egr3 is required for activity-dependent expression of genes involved in the DNA damage response. Our findings show that EGR3 is critical for the expression of genes that are mis-expressed in schizophrenia and reveal a novel requirement for EGR3 in the expression of genes involved in activity-induced DNA damage response.

MRI findings as markers of idiopathic intracranial hypertension.

PURPOSE OF REVIEW: Negative findings on neuroimaging are part of the diagnostic criteria for idiopathic intracranial hypertension (IIH), a syndrome characterized by increased intracranial pressure (ICP). Some positive neuroimaging findings are associated with increased ICP, but their role in diagnosis of IIH has not been established. We provide an overview of these findings and their relevance for diagnosis of raised intracranial pressure. RECENT FINDINGS: MRI acquisition techniques have significantly improved in the last few decades leading to better characterization of the intracranial changes associated with IIH, including empty sella turcica, optic nerve tortuosity, distension of the optic nerve sheath, posterior globe flattening, slit-like ventricles, and venous sinus stenosis. These may be MRI biomarkers of increased ICP. Prevalence difference between people with and without increased ICP, and reversibility of these MRI findings following treatment of increased ICP inform evaluation of their diagnostic potential. SUMMARY: MRI and magnetic resonance venography findings are important tools in the diagnosis of IIH. Empty sella turcica, optic nerve protrusion, distension of the optic nerve sheath, optic nerve tortuosity, posterior globe flattening, and transverse sinus stenosis have been found to be the most promising diagnostic markers for IIH, although absence of these findings does not rule out the diagnosis.