Early life stress is known to have a profound effect on both human's and animal's ability to learn from aversive stimuli. Studies in our lab have shown that early life stress accelerates the development of limbic structure. However, the underlying molecular mechanism of this acceleration remains largely unknown. Recent investigation of brain development and synaptic plasticity as well as studies of the development of aversive learning have demonstrated the necessity of brain-derived neurotrophic factor (BDNF) in the development and regulation of limbic function. This in combination with recent findings from our lab, showing accelerated parvalbumin generation (a BDNF-initiated process), led us to hypothesize that ELS serves to elevate BDNF and drives the acceleration in limbic system development. To test this hypothesis, we subjected mice to an early life stress paradigm, which consisted of reducing maternal access to bedding and nesting materials from postnatal days 4 to 11. ELS and control mice were then euthanized at multiple time points extending from early childhood into adulthood, their brains extracted and analyzed for mRNA quantification of BDNF and BDNF receptors. We found that mice exposed to ELS showed elevated levels of BDNF mRNA shortly following the completion of stress, relative to control-reared animals. This peak in BDNF was associated with earlier expression of several markers of circuit development. To test if this elevation in BDNF is in fact contributing to accelerated brain development, we are using a genetic approach in which we attempt to simulate ELS by genetically eliminating the TrkB-T1 receptor (an endogenous dominant negative receptor for BDNF). TrkB-T1 KO mice were tested both for behavioral and biochemical markers of accelerated development, with measurements occurring at postnatal days 16, 21, 28, and 50.
"BDNF: a potential driver of early stress associated neurobehavioral development"
Summer Research Symposium.
Brown Digital Repository. Brown University Library.
Each year, Brown University showcases the research of its undergraduates at the Summer Research Symposium. More than half of the student-researchers are UTRA recipients, while others receive funding from a variety of Brown-administered and national programs and fellowships and go …