Original Article

Neuropsychopharmacology (2008) 33, 378–393; doi:10.1038/sj.npp.1301397; published online 11 April 2007

Exposure to Stressors during Juvenility Disrupts Development-Related Alterations in the PSA-NCAM to NCAM Expression Ratio: Potential Relevance for Mood and Anxiety Disorders

Michael Tsoory1, Adi Guterman1 and Gal Richter-Levin1

1Department of Psychology, The Brain and Behavior Research Center, University of Haifa, Mount Carmel, Haifa, Israel

Correspondence: Professor G Richter-Levin, Department of Psychology, The Brain and Behavior Research Center, University of Haifa, Mount Carmel, Haifa 31905, Israel. Tel: +972 4 824 0962; Fax: +972 4 828 8578; E-mail: gal.r-l@psy.haifa.ac.il

Received 6 July 2006; Revised 6 February 2007; Accepted 13 February 2007; Published online 11 April 2007.

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Abstract

Childhood trauma is associated with higher rates of both mood and anxiety disorders in adulthood. The exposure of rats to stressors during juvenility has comparable effects, and was suggested as a model of induced predisposition for these disorders. The neural cell adhesion molecule (NCAM) and its polysialylated form PSA-NCAM are critically involved in neural development, activity-dependent synaptic plasticity, and learning processes. We examined the effects of exposure to stressors during juvenility on coping with stressors in adulthood and on NCAM and PSA-NCAM expression within the rat limbic system both soon after the exposure and in adulthood. Exposure to stressors during juvenility reduced novel-setting exploration and impaired two-way shuttle avoidance learning in adulthood. Among naive rats, a development-related decrease of about 50% was evident in the PSA-NCAM to NCAM expression ratio in the basolateral amygdala, in the CA1 and dentate gyrus regions of the hippocampus, and in the entorhinal cortex. In juvenile-stressed rats, we found no such decrease, but rather an increase in the polysialylation of NCAM (~50%), evident soon after the exposure to juvenile stress and also in adulthood. Our results suggest that exposure to stressors during juvenility alters the maturation of the limbic system, and potentially underlies the predisposition to exhibit stress-related symptoms in adulthood.

Keywords:

juvenile rats, early life stress, NCAM, PSA-NCAM, anxiety disorders, mood disorders

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