“Juvenile stress” alters maturation-related changes in expression of the neural cell adhesion molecule L1 in the limbic system: Relevance for stress-related psychopathologies

Department of Psychology, University of Haifa, Haifa, Israel.
Journal of Neuroscience Research (Impact Factor: 2.59). 02/2010; 88(2):369-80. DOI: 10.1002/jnr.22203
Source: PubMed


L1 is critically involved in neural development and maturation, activity-dependent synaptic plasticity, and learning processes. Among adult rats, chronic stress protocols that affect L1 functioning also induce impaired cognitive and neural functioning and heightened anxiety reminiscent of stress-induced mood and anxiety disorders. Epidemiological studies indicate that childhood trauma is related predominantly to higher rates of both mood and anxiety disorders in adulthood and is associated with altered limbic system functioning. Exposing rats to stress during the juvenile period ("juvenile stress") has comparable effects and was suggested as a model of induced predisposition for these disorders. This study examined the effects of juvenile stress on rats aversive learning and on L1 expression soon after exposure and in adulthood, both following additional exposure to acute stress and in its absence. Adult juvenile-stressed rats exhibited enhanced cued fear conditioning, reduced novel-setting exploration, and impaired avoidance learning. Furthermore, juvenile stress increased L1 expression in the BLA, CA1, DG, and EC both soon after the stressful experience and during adulthood. It appears that juvenile stress affects the normative maturational decrease in L1 expression. The results support previous indications that juvenile stress alters the maturation of the limbic system and further support a role for L1 regulation in the mechanisms that underlie the predisposition to exhibit mood and/or anxiety disorders in adulthood. Furthermore, the findings support the "network hypothesis," which postulates that information-processing problems within relevant neural networks might underlie stress-induced mood and anxiety disorders.

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    • "Alternatively, it is possible that like the stronger fear conditioning observed in stressed animals (e.g. Giachero et al., 2013; Rau & Fanselow, 2009; Rau et al., 2005 but see Tsoory et al., 2010), individuals with repeated exposure to trauma make stronger context–outcome associations when negative outcomes are involved. These stronger associations may then be more difficult to reverse. "
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    ABSTRACT: Abstract Neuroimaging studies have demonstrated reduced hippocampal volume in trauma-exposed individuals without PTSD. However the implications of such a deficit in this non-clinical population is still unclear. Animal and human models of PTSD suggest that hippocampal deficit may result in impaired learning and use of associations between contextual information and aversive events. Previous study has shown that individuals with PTSD have a selective impairment in reversing the negative outcome of context related information. The aim of the present study was to test whether non-PTSD individuals who are repeatedly exposed to traumatic events display similar impairment. To that end, we compared the performance of active-duty firefighters who are frequently exposed to traumatic events as part of their occupational routine and civilian matched-controls with no history of trauma-exposure. We used a novel cue-context reversal paradigm, which separately evaluates reversal of negative and positive outcomes of cue and context related information. As predicted, we found that while both trauma-exposed firefighters and unexposed matched-controls were able to acquire and retain stimulus-outcome associations, firefighters struggled to learn that a previously negative context is later associated with a positive outcome. This impairment did not correlate with levels of PTSD, anxiety or depressive symptoms. The results suggest that similar to individuals with PTSD, highly exposed individuals fail to associate traumatic outcomes with their appropriate context. This impairment may reflect a possible hidden price of repeated traumatic exposure, which is not necessarily associated with PTSD diagnosis, and may affect the way highly exposed-individuals interpret and react to their environment.
    Full-text · Article · May 2014 · Stress (Amsterdam, Netherlands)
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    • "The juvenile brain experiences dramatic changes in structure and function as it matures (Romeo and McEwen 2006), and epidemiological studies have linked juvenile stress (JS) with the development of depression , anxiety, and PTSD, as well as suicide attempts later in life (Morgan et al. 2003; Kausch et al. 2006; Weich et al. 2009). In animal models, JS increases anxiety behavior, alters fear conditioning, learning, and memory (Avital and Richter-Levin 2005; Toledo-Rodriguez and Sandi 2007; Tsoory et al. 2007; Jacobson-Pick and Richter-Levin 2010; Brydges et al. 2012, 2013), remodels corticolimbic architecture (Eiland et al. 2012), and alters neural gene expression in adulthood (Jacobson-Pick et al. 2008; Tsoory et al. 2010). Effects on behavior are observed when animals experience stress in adulthood, but they are significantly enhanced when stress is given in the juvenile phase (Avital and Richter-Levin 2005; Tsoory and Richter-Levin 2006), demonstrating phase specific changes. "
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    ABSTRACT: Exposure to stress in early life is correlated with the development of anxiety disorders in adulthood. The underlying mechanisms are not fully understood, but an imbalance in corticosteroid receptor (CR) expression in the limbic system, particularly the hippocampus, has been implicated in the etiology of anxiety disorders. However, little is known about how prepubertal stress in the so called "juvenile" period might alter the expression of these receptors. Therefore, the aim of this study was to investigate how stress experienced in the juvenile phase of life altered hippocampal expression of CRs and anxiety behaviors in adulthood. We used a rodent model to assess the effects of juvenile stress on hippocampal CR expression, and performance in three behavioral tests of anxiety in adulthood. Juvenile stress (JS) increased anxiety-like behavior on the elevated plus maze, increased mineralocorticoid receptor (MR) expression, and decreased the ratio of glucocorticoid receptor (GR) to MR expression in the hippocampus of adult animals. Females demonstrated lower levels of anxiety-type behavior and increased activity in three behavioral tests, and had greater expression of GR and GR:MR ratio than males, regardless of treatment. These results demonstrate that JS can alter the expression and balance of CRs, providing a potential mechanism for the corresponding increase in anxiety behavior observed in adulthood. Further evidence for the role of CR expression in anxiety is provided by sex differences in anxiety behavior and corresponding alterations in CR expression.
    Full-text · Article · Mar 2014 · Brain and Behavior
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    • "In studies investigating fear conditioning in adulthood after exposure to stressors in adolescence in rodents, it is generally found that male rats stressed in adolescence exhibit more robust fear conditioning in adulthood (greater freezing to cue, context, or resistance to extinction relative to controls) (Toledo-Rodriguez & Sandi, 2007; Tsoory et al., 2010; Yee et al., 2012). In contrast, we found that social instability stress (change of cage partners after one hour isolation daily from postnatal day 30–45) reduced freezing to both the conditioning context and the cue in adult males compared to controls (Morrissey et al., 2011). "
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    ABSTRACT: Abstract We previously observed that social instability stress (SS: daily 1 h isolation and change of cage partners for 16 days) in adolescence, but not in adulthood, decreased context and cue memory after fear conditioning in male rats. Effects of stress are typically sex-specific, and so here we investigated adolescent and adult SS effects in females on the strength of acquired contextual and cued fear conditioning, as well as extinction learning, beginning either the day after the stress procedure or four weeks later. For SS in adolescence, SS females spent more time freezing (fear measure) during extinction than did controls, whereas SS in adulthood had no effect on any measure of fear conditioning. The results also indicated an effect of age: females in late adolescence show more rapid extinction of cue and better memory of extinction of context compared to adult females, which may indicate resilience to acute footshock in adolescence. Thus fear circuitry continues to mature into late adolescence, which may underlie the heightened plasticity in response to chronic stressors of adolescents compared to adults.
    Full-text · Article · Sep 2013 · Stress (Amsterdam, Netherlands)
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