Unexpected Transcriptional Programs Contribute to Hippocampal Memory Deficits and Neuronal Stunting after Early-Life Adversity.
作者： Jessica L. Bolton , Anton Schulmann , Megan M. Garcia-Curran , Limor Regev , Yuncai Chen
DOI: 10.1016/J.CELREP.2020.108511
关键词: Transcription factor 、 Epigenetics 、 Transcriptional regulation 、 Glucocorticoid receptor 、 Biology 、 Gene expression 、 Gene 、 Neuroscience 、 Hippocampus 、 Hippocampal formation
摘要: Early-life adversity (ELA) is associated with lifelong memory deficits, yet the responsible mechanisms remain unclear. We impose ELA by rearing rat pups in simulated poverty, assess hippocampal memory, and probe changes gene expression, their transcriptional regulation, consequent neuronal structure. rats have poor stunted pyramidal neurons ~140 differentially expressed genes. Upstream regulators of altered genes include glucocorticoid receptor and, unexpectedly, transcription factor neuron-restrictive silencer (NRSF/REST). NRSF contributes critically to deficits because blocking its function transiently following rescues spatial restores dendritic arborization rats. Blocking in vitro augments complexity developing neurons, suggesting that represses involved maturation. These findings establish important, surprising contributions ELA-induced programming disrupts maturation function.
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