Yuncai Chen

Yuncai Chen, Ph.D., Young Investigator 2005

Yuncai Chen, Ph.D., 2005

Yuncai Chen, Ph.D., 2005NARSAD: Research Center: Project Summary for Yuncai Chen, Ph.D.
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Yuncai Chen, Ph.D. (Young Investigator 2005) of the University of California at Irvine, plans to study in animal models how stress creates structural changes in the brain that may contribute to the development of schizophrenia.Schizophrenia is likely a combinatorial result of genetic and environmental factors.Among the latter, early-life stress, resulting from pre-, peri- and postnatal adverse events is highly linked to the development of schizophrenia.Thus, molecules activated by stress in the developing brain may contribute to the neuronal dysfunction in schizophrenia.The stress modulator, corticotropin releasing hormone (CRH), is highly expressed in developing hippocampus and neocortex and Dr. Chen previously has found that CRH is released into synaptic clefts by early-life stress and interacts with specific receptors to influence hippocampal neuronal function.New data demonstrate that chronic exposure to CRH can also affect neuronal connectivity and lead to excessive dendritic pruning, or remodeling of dendrites.In this proposal, Dr. Chen aims to test whether early-life stress may release hippocampal (and perhaps neocortical) CRH in excessive amounts and lead to excessive pruning, reduced spine formation and subnormal synaptic connectivity, as is found in schizophrenia.Dr. Chen will culture hippocampi from normal neonatal rats in the presence of excessive CRH or of a selective receptor antagonist and evaluate the development of dendritic trees and spines.Dr. Chen also will visualize in real-time dendritic changes in response to CRH using fluorescent protein tagging.And Dr. Chen will use transgenic mice deficient in the selective CRH receptor, CRF1, to test whether they have exuberant dendritic trees (as implied by the pilot data).