Hippocampal Dysfunction and Cognitive Impairments Provoked by Chronic Early-Life Stress Involve Excessive Activation of CRH Receptors

• DOI: 10.1523/jneurosci.1784-10.2010
• Publication Date: 2010-09-29T17:17:31Z
• Authors: Autumn S. Ivy; Christopher S. Rex; Yuncai Chen; Céline Dubé; Pamela M. Maras; Dimitri E. Grigor...; Christine M. Gall; Gary Lynch; Tallie Z. Baram
• Keywords: Chronic Stress; Corticotropin-releasing hormone

Chronic stress impairs learning and memory in humans rodents disrupts long-term potentiation (LTP) animal models. These effects are associated with structural changes hippocampal neurons, including reduced dendritic arborization. Unlike the generally reversible of chronic on adult rat hippocampus, we have previously found that early-life endure worsen during adulthood, yet mechanisms for these clinically important sequelae poorly understood. Stress promotes secretion neuropeptide corticotropin-releasing hormone (CRH) from interneurons, activating receptors (CRF 1 ) located pyramidal cell dendrites. Additionally, CRF occupancy negatively affects arborization mouse organotypic slice cultures, similar to pattern observed middle-aged, early-stressed (CES) rats. Here CRH expression is augmented hippocampus middle-aged CES rats, then tested whether morphological defects poor performance animals involve excessive activation receptors. Central or peripheral administration a blocker following period improved rats novel-object recognition tests Morris water maze. Consonant effects, antagonist also prevented atrophy LTP attenuation CA1 Schaffer collateral synapses. Together, data suggest persistently elevated CRH–CRF interaction contributes importantly cognitive impairments stress. Reducing post hoc normalized function middle age, thus offering potential mechanism-based therapeutic interventions children affected by