Correlated memory defects and hippocampal dendritic spine loss after acute stress involve corticotropin-releasing hormone signaling
Open Access
- 6 July 2010
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 107 (29), 13123-13128
- https://doi.org/10.1073/pnas.1003825107
Abstract
Stress affects the hippocampus, a brain region crucial for memory. In rodents, acute stress may reduce density of dendritic spines, the location of postsynaptic elements of excitatory synapses, and impair long-term potentiation and memory. Steroid stress hormones and neurotransmitters have been implicated in the underlying mechanisms, but the role of corticotropin-releasing hormone (CRH), a hypothalamic hormone also released during stress within hippocampus, has not been elucidated. In addition, the causal relationship of spine loss and memory defects after acute stress is unclear. We used transgenic mice that expressed YFP in hippocampal neurons and found that a 5-h stress resulted in profound loss of learning and memory. This deficit was associated with selective disruption of long-term potentiation and of dendritic spine integrity in commissural/associational pathways of hippocampal area CA3. The degree of memory deficit in individual mice correlated significantly with the reduced density of area CA3 apical dendritic spines in the same mice. Moreover, administration of the CRH receptor type 1 (CRFR(1)) blocker NBI 30775 directly into the brain prevented the stress-induced spine loss and restored the stress-impaired cognitive functions. We conclude that acute, hours-long stress impairs learning and memory via mechanisms that disrupt the integrity of hippocampal dendritic spines. In addition, establishing the contribution of hippocampal CRH-CRFR(1) signaling to these processes highlights the complexity of the orchestrated mechanisms by which stress impacts hippocampal structure and function.Keywords
This publication has 91 references indexed in Scilit:
- Structural and functional alterations to rat medial prefrontal cortex following chronic restraint stress and recoveryNeuroscience, 2009
- Stressful experience has opposite effects on dendritic spines in the hippocampus of cycling versus masculinized femalesNeuroscience Letters, 2009
- The substrates of memory: Defects, treatments, and enhancementEuropean Journal of Pharmacology, 2008
- Vasopressin: Behavioral roles of an “original” neuropeptideProgress in Neurobiology, 2008
- Structural and functional plasticity of the human brain in posttraumatic stress disorderProgress in Brain Research, 2007
- Recognition memory and the medial temporal lobe: a new perspectiveNature Reviews Neuroscience, 2007
- Plasticity-Induced Growth of Dendritic Spines by Exocytic Trafficking from Recycling EndosomesNeuron, 2006
- Hippocampal neuroplasticity induced by early-life stress: Functional and molecular aspectsFrontiers in Neuroendocrinology, 2006
- Stress and the brain: from adaptation to diseaseNature Reviews Neuroscience, 2005
- Dendritic spines and long-term plasticityNature Reviews Neuroscience, 2005