"Juvenile Stress" Alters Maturation-Related Changes in Expression of the Neural Cell Adhesion Molecule L1 in the Limbic System: Relevance for Stress-Related Psychopathologies

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. (C) 2009 Wiley-Liss, Inc.