Dengke Ma Talks About Gadd45b
Fast Moving Front Commentary, November 2010
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Article: Neuronal Activity-Induced Gadd45b Promotes Epigenetic DNA Demethylation and Adult Neurogenesis
Authors: Ma, DK;Jang, MH;Guo,
JU;Kitabatake, Y;Chang, ML;Pow-Anpongkul, N;Flavell, RA;Lu,
B;Ming, GL;Song, H |
Dengke Ma talks with ScienceWatch.com and answers a few questions about this month's Fast Moving Fronts paper in the field of Neuroscience & Behavior.
Why do you think your paper is highly
cited?
This paper links an activity-inducible gene to epigenetic DNA modifications in neurons and suggests its functional roles in long-lasting modulation of adult neurogenesis. It covers several interesting domains of study, including epigenetics, adult neurogenesis, plasticity, and antidepressant treatment.
Reversible neuronal DNA methylation in the mammalian nervous system has been previously implicated, but its molecular mechanisms and functional significance remain largely unclear. Focusing on adult neurogenesis, which represents a striking example of activity-dependent neural plasticity, we identified Gadd45b as a crucial mediator that translates transient neuronal activity stimuli to lasting epigenetic DNA modifications in neurons, with specific functional impact on activity-regulated aspects of adult neurogenesis. Our studies also support emerging lines of evidence that active DNA demethylation in mammals can occur through DNA excision repair-like mechanisms.
Does it describe a new discovery, methodology, or
synthesis of knowledge?
"Antidepressants and electroconvulsive treatments (ECT) dramatically enhance adult neurogenesis, which has been suggested to mediate the effect of antidepressants."
This paper describes a new discovery and synthesis of knowledge from several areas of biology.
Would you summarize the significance of your paper
in layman's terms?
New neurons can be continuously generated in discrete regions of the adult brain; this process is dynamically modulated by a variety of environmental and internal stimuli to the brain. The mechanism by which transient stimuli produce lasting effects on adult neurogenesis appears to occur, at least in part, through DNA modification of several genes in pre-existing neurons. Enhanced expression of these genes promotes continuous addition of new neurons to the brain.
How did you become involved in this research, and
how would you describe the particular challenges, setbacks, and
successes that you've encountered along the way?
We initiated an expression screen for epigenetic regulators of adult neurogenesis and found the striking induction of Gadd45b by neuronal activity. One particular challenge was to acutely isolate a sufficient amount of relatively homogenous cell population in vivo for DNA methylation analysis, and we succeeded by optimizing isolation procedures and attempting several then recently improved analytic techniques.
Where do you see your research leading in the
future?
We anticipate more mechanistic investigation into the epigenetic DNA modifications in both developing and mature neurons to facilitate insights into neuronal gene regulation and plasticity at the molecular and behavioral level.
Do you foresee any social or political
implications for your research?
Antidepressants and electroconvulsive treatments (ECT) dramatically enhance
adult neurogenesis, which has been suggested to mediate the effect of
antidepressants. Gadd45b is strongly activated by ECT and required for
ECT-induced adult neurogenesis. This suggests its potential role in
mediating antidepressant effects and further implicates epigenetic
mechanisms through changes of DNA methylation in the pathological process
contributing to depression.
Dengke Ma
Helen Hay Whitney Fellow
Department of Biology
Massachusetts Institute of Technology
Boston, MA, USA
KEYWORDS: GENE-EXPRESSION; MESSENGER-RNA; MOUSE; TRANSCRIPTION; METHYLATION; MECHANISMS; PLASTICITY; SIGNALS; PROTEIN; CORTEX.