Identification of Early Biomarkers for Alcohol Related Brain Development Abnormalities
Dr Nune Darbinian discusses latest research findings at Shriners Hospitals Pediatric Research Center
17 Jul 2016
Dr Nune Darbinian, Research Laboratory Manager at Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine at Temple University, told SelectScience about brain development research that was recently presented at the Fetal Alcohol Spectrum Disorders Study Group/Research Society on Alcoholism (FASDSG/RSoA) and Society for Neuroscience (SfN) symposia.
Image: synapsis - Copyright Sebastian Kaulitzki
Dr Darbinian’s neurodevelopmental research encompasses both the effects of neuroprotective proteins, such as DING phosphatases, and the effects of neurotoxins, in particular, alcohol and the study of Fetal Alcohol Syndrome (FAS).
Shriners Hospitals Pediatric Research Center The Center is a collaboration between the Shriners Hospitals for Children and Temple University School of Medicine. The mission of the Center is to do research that will develop therapies for injuries to the nervous system in children, focusing on mechanisms of neural repair and plasticity
Fetal Alcohol Syndrome causes neurodevelopmental abnormalities
FAS, caused by prenatal alcohol exposure, is associated with eye developmental abnormalities but the precise mechanisms underlying in utero neuronal injury have yet to be fully elucidated. Dr Darbinian recently reported, at the RSoA symposium, that eye defects related to prenatal alcohol exposure could be detected in humans as early as 16-weeks of gestation. Although not yet curable, this may provide a useful biomarker of in utero responses to potential treatments of FAS.
Investigating molecular mechanisms of FAS
Dr Darbinian is investigating the molecular mechanisms underlying FAS by examining the destruction and formation of oligodendrocytes and the formation of demyelinated lesions using an in vivo FAS model to study brain developmental abnormalities and have reported on the associated markers, which indicate the involvement of multiple pathways in alcohol induced-neurotoxicity.
In addition, recent data have shown that the neuroprotective agent pDING phosphatase may provide a basis for FAS therapy. Not only for the prevention of neuronal injury but also to reduce neuronal damage associated with alcohol toxicity later in life.
Flow cytometry analysis, using the Guava flow cytometer, will be important to confirm specific regional brain damage and cell-type injury.
Dr. Nune Darbinian Shriners Hospitals Pediatric Research Center
To investigate these mechanisms Dr. Darbinian uses a combination of gene and protein expression analysis tools and techniques. Gene expression is probed using RT-PCR, quantitative PCR and digital PCR. Protein expression is analyzed using immunohistochemistry on brain samples, quantitative Western blotting, ELISA and flow cytometry using MilliporeSigma’s Guava easyCyte™ systems.
Future perspectives
Using these techniques, the team hope to identify mechanisms underlying neurodevelopmental abnormalities, which may contribute to the development of targeted drug therapies, for FAS and related conditions.