Hippocampal neuroplasticity induced by early-life stress: Functional and molecular aspects

Abstract

Whereas genetic factors contribute crucially to brain function, early-life events, including stress, exert long-lasting influence on neuronal function. Here, we focus on the hippocampus as the target of these early-life events because of its crucial role in learning and memory. Using a novel immaturerodent model, we describe the deleterious consequences of chronic early-life 'psychological' stress on hippocampus-dependent cognitive tasks. We review the cellular mechanisms involved and discuss the roles of stress-mediating molecules, including corticotropin releasing hormone, in the process by which stress impacts the structure and function of hippocampal neurons. KeywordsNeonatal; Rat; Human; Stress; Memory; Hippocampus; Corticotropin releasing hormone; CRF; Hypothalamic pituitary adrenal axis; Neuroplasticity Early-life events interact with genetic factors to influence hippocampal function long-termBrain function and dysfunction throughout life are determined by the interaction of genetic factors with 'acquired' environmental events, signals and stimuli [100]. Events that occur early in life are capable of exerting effects that persist throughout adulthood. Here, we focus on the hippocampus as the target of these early-life events because of its crucial role in learning, memory storage and retrieval, and general cognitive function [105,41,65]. Indeed, early-life events, via complex interactions with genetic factors [106,120], have been suspected to be a major determinant of smaller hippocampal volume and long-term cognitive dysfunction in preterm infants [111,17] and may play a role in certain affective and dementing disorders in the adult and aging human [100,26,120]. This review focuses on the mechanisms by which certain early-life events influence populations of hippocampal neurons acutely, and impact the function and integrity of the hippocampus long-term. Studying early-life stress may be used to probe the molecular mechanisms involved in experience-evoked hippocampal neuroplasticityStress may provide a salient example of early-life experience that might exert long-lasting influence on the brain, because (1) over 50% of the world's children are exposed to stress [139] and (2) evidence from both human and animal studies suggests that early-life stress has profound effects on cognitive function and emotional health.Stress has been shown to influence the hippocampus in a number of important ways. Whereas acute mild stress rapidly enhances synaptic efficacy and learning and memory processes [131,45,91,123], chronic or severe activation of the stress response early in life has been shown to be potentially injurious in both humans [6,120,147] and experimental animals [120,31]. For example, severe childhood psychological stress (neglect and abuse) correlates with a higher incidence of learning disabilities later in life, including those learning and memory functions requiring an intact hippocampus [121,50]. Further, MRI studies have suggested that adults subjected to abuse (a measure of chronic stress) ...

CRHR1 links peripuberty stress with deficits in social and stress-coping behaviors

“…While we find no changes in Crhr2 expression in our study, data from previous maternal stress studies in rodents yielded mixed results regarding changes in the central expression of this gene (Vazquez et al, 2003;Plotsky et al, 2005;Bravo et al, 2011). In line with our findings, increased Crhr1 mRNA expression in the amygdala (Bravo et al, 2011) and hippocampus (Fenoglio et al, 2006;Ivy et al, 2010;O'Malley et al, 2011) was also found in adult rodents subjected to maternal stress during the early postnatal period. In addition, previous evidence focused in the dorsal raphe nucleus identified juvenility and adolescence as periods of vulnerability for the modulation of the CRH system by stress (Lukkes et al, 2009).…”

“…Furthermore, increasing CRH drive occurring specifically in the central amygdala through lentiviral-induced neuropeptide overexpression was also found to enhance anxiety-like (Flandreau et al, 2012) and depression-like (Keen-Rhinehart et al, 2009) behaviors in rats. Enhanced CRHR1 expression in the hippocampus has been linked with impaired cognitive function induced by early life stress (Fenoglio et al, 2006;Ivy et al, 2010).…”

“…In rodents, early life stress e induced during the very early postnatal period by either maternal separation or unstable maternal care e was found to lead to increased anxiety-like behaviors and cognitive deficits in association with increased central CRH and CRHR1 expression (Plotsky et al, 2005;Fenoglio et al, 2006;Ivy et al, 2010;Wang et al, 2011Wang et al, , 2012. Manipulation of the CRHR1 system during development during the aftermath of early life stress exposure was found to prevent some of the longterm behavioral alterations observed at adulthood.…”

Cellular and molecular mechanisms of hippocampal activation by acute stress are age-dependent

“…It is well established that the effects of stress on the central nervous system vary as a function of the age at which stress is imposed (reviewed in McEwen, 1 Sanchez et al, 2 Welberg and Seckl, 3 Avishai-Eilner et al, 4 Levine, 5 Miller and O'Callaghan 6 and Fenoglio et al 7 ). For example, prenatal stress has been shown to 're-program' or 'imprint' both neuroendocrine and behavioral responses to subsequent stress throughout the lifetime (see Avishai-Eilner et al, 4 Fenoglio et al, 7 Wadhwa et al, 8 Welberg et al 9 and Weinstock 10 for recent reviews).…”

“…For example, prenatal stress has been shown to 're-program' or 'imprint' both neuroendocrine and behavioral responses to subsequent stress throughout the lifetime (see Avishai-Eilner et al, 4 Fenoglio et al, 7 Wadhwa et al, 8 Welberg et al 9 and Weinstock 10 for recent reviews). Neuroendocrine activation in response to stress also varies as a function of age.…”