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Published on: April 11, 2019
Differential Gene Expression Profile Induced by Valproic Acid (VPA) in Pediatric Epileptic Patients
Esaú Floriano-Sánchez1, Fernando Brindis2, Daniel Ortega-Cuellar3
1Multidisciplinary Research Laboratory, Military Graduate School of Health, SEDENA, 11200 Mexico City, Mexico. florianoesa@hotmail.com.
Insights
Early identification of childhood epilepsy may be possible using gene expression biomarkers. Research found that cAMP-response element binding protein (CREB) and leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) are key in epilepsy development, with valproic acid treatment showing promise.
Area of Science:
- Neuroscience
- Genetics
- Biomarker Discovery
Background:
- Epilepsy affects millions globally, necessitating early diagnostic biomarkers for effective childhood treatment.
- Understanding the genetic underpinnings of epilepsy is crucial for developing targeted therapies.
Purpose of the Study:
- To identify differentially expressed genes in children with epilepsy using whole-genome microarray analysis.
- To investigate the role of specific genes, such as CREB and LAIR1, in epilepsy pathogenesis.
- To evaluate the potential of valproic acid (VPA) treatment in reversing gene expression changes associated with epilepsy.
Main Methods:
- Whole-genome microarray analysis of blood cells from epileptic children (with and without VPA treatment) and healthy controls.
- Identification and analysis of significantly differentially expressed genes.
- Functional analysis to understand gene interactions and pathways involved in epilepsy.
Main Results:
- Overexpression of cAMP-response element binding protein (CREB) was observed in epileptic children compared to controls.
- Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) was significantly upregulated in epileptic patients and its expression was reversed by VPA treatment.
- VPA treatment for 6 and 12 months reversed several gene expression changes, including the upregulation of LAIR1, suggesting a disruption of the LAIR1-CREB complex.
Conclusions:
- CREB and LAIR1 may play a critical role in epilepsy development, potentially through an activated LAIR1-CREB complex.
- VPA treatment appears to repress disease-associated genes by disrupting this complex, leading to successful therapeutic outcomes.
- Microarray analysis provides valuable insights for novel biomarker discovery for early epilepsy detection in children.
Abstract:
Epilepsy is a neuronal disease that affects up to 70 million people worldwide. The development of effective therapies to combat childhood epilepsy requires early biomarkers. Here, we performed a whole-genome microarray analysis in blood cells to identify genes differentially expressed between epileptic and epileptic valproic acid (VPA)-treated children versus normal children to obtain information about the gene expression to help us to understand genetic aspects of this disease. We found that the most significant differentially expressed genes were related to the transcriptional factor cAMP-response element binding protein (CREB) that is overexpressed in children with epilepsy compared with normal children, and 6 and 12 months of VPA treatment reversed several of these changes. Interestingly, leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), a type I transmembrane glycoprotein that binds collagen proteins and contains CREB binding sites, was one of the more up-regulated genes in epileptic patients, and treatment with VPA strongly reversed its up-regulation. CREB up-regulates genes related to epilepsy; here, we suggest that LAIR1 could activate CREB, and together, they trigger epilepsy. After VPA treatment, LAIR1 repressed genes by disrupting the functional LAIR1⁻CREB complex, resulting in successful treatment. A functional microarray analysis offers new information that could open novel avenues of research in biomarker discovery, which may be useful for the early identification of children with a predisposition to epilepsy.
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