Author contributions: X.-D.W. and M.V.S. designed the experiments; X.-M.L., X.-D.Y, J.J., J.-T.L., and X.-M.X. performed the experiments; X.-M.L., X.-D.Y., J.J., and X.-D.W. analyzed the data; Y.-A.S., T.-M.S. and X.-D.W. supervised the experiments; X.-M.L., M.V.S., T.-M.S., and X.-D.W. wrote the paper.
Blockade of corticotropin-releasing hormone receptor 1 attenuates early-life stress-induced synaptic abnormalities in the neonatal hippocampus
Version of Record online: 18 FEB 2014
Copyright © 2014 Wiley Periodicals, Inc.
Volume 24, Issue 5, pages 528–540, May 2014
How to Cite
Liao, X.-M., Yang, X.-D., Jia, J., Li, J.-T., Xie, X.-M., Su, Y.-A., Schmidt, M. V., Si, T.-M. and Wang, X.-D. (2014), Blockade of corticotropin-releasing hormone receptor 1 attenuates early-life stress-induced synaptic abnormalities in the neonatal hippocampus. Hippocampus, 24: 528–540. doi: 10.1002/hipo.22254
- Issue online: 4 APR 2014
- Version of Record online: 18 FEB 2014
- Accepted manuscript online: 3 FEB 2014 12:45PM EST
- Manuscript Accepted: 24 JAN 2014
- Manuscript Revised: 5 JAN 2014
- Manuscript Received: 17 OCT 2013
- National Natural Science Foundation of China. Grant Numbers: 81171284, 30800361, 81301152
- Research Fund for the Doctoral Program of Higher Education of China. Grant Number: 20120001110046
- International Brain Research Organization
- early-life stress;
- corticotropin-releasing hormone receptor 1;
- glucocorticoid receptors;
Adult individuals with early stressful experience exhibit impaired hippocampal neuronal morphology, synaptic plasticity and cognitive performance. While our knowledge on the persistent effects of early-life stress on hippocampal structure and function and the underlying mechanisms has advanced over the recent years, the molecular basis of the immediate postnatal stress effects on hippocampal development remains to be investigated. Here, we reported that repeated blockade of corticotropin-releasing hormone receptor 1 (CRHR1) ameliorated postnatal stress-induced hippocampal synaptic abnormalities in neonatal mice. Following the stress exposure, pups with fragmented maternal care showed retarded dendritic outgrowth and spine formation in CA3 pyramidal neurons and reduced hippocampal levels of synapse-related proteins. During the stress exposure, repeated blockade of glucocorticoid receptors (GRs) by daily administration of RU486 (100 µg g−1) failed to attenuate postnatal stress-evoked synaptic impairments. Conversely, daily administration of the CRHR1 antagonist antalarmin hydrochloride (20 µg g−1) in stressed pups normalized hippocampal protein levels of synaptophysin, postsynaptic density-95, nectin-1, and nectin-3, but not the N-methyl-d-aspartate receptor subunits NR1 and NR2A. Additionally, GR or CRHR1 antagonism attenuated postnatal stress-induced endocrine alterations but not body growth retardation. Our data indicate that the CRH-CRHR1 system modulates the deleterious effects of early-life stress on dendritic development, spinogenesis, and synapse formation, and that early interventions of this system may prevent stress-induced hippocampal maldevelopment. © 2014 Wiley Periodicals, Inc.