This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goel, N. Articles by Bale, T. L. Search for Related Content PubMed PubMed Citation Articles by Goel, N. Articles by Bale, T. L.

Identifying Early Behavioral and Molecular Markers of Future Stress Sensitivity

Department of Animal Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Address all correspondence and requests for reprints to: Tracy L. Bale, University of Pennsylvania, 201E Vet, 6046, 3800 Spruce Street, Philadelphia, Pennsylvania 19104. E-mail: tbale{at}vet.upenn.edu.

Puberty is a plastic period of neurological development when critical maturation of stress pathways occurs. Abnormal maturation may be predictive of future stress sensitivity and affective disorder risk. To identify potential early markers of stress-related disease predisposition, we examined physiological and behavioral stress responses in male pubertal mice compared with adults, using a genetic model of elevated stress sensitivity, CRF receptor-2 (CRFR2)-deficient mice. Juvenile mice of both genotypes exhibited greater basal and stress-induced corticosterone levels than adult mice, indicating that overall hypothalamic-pituitary-adrenal axis sensitivity diminishes in adulthood. However, juvenile CRFR2-deficient mice displayed a delayed stress recovery typical of adults of this genotype, suggesting an early marker of stress sensitivity. The adult phenotype of reduced hippocampal glucocorticoid receptor expression in these sensitive mice was also detected during puberty. This reduction may account for an impaired hypothalamic-pituitary-adrenal axis negative feedback and as such be an early indicator of a stress-sensitive phenotype. Examination of behavioral responses to stress revealed that CRFR2-deficient mice show exaggerated postpubertal maturation. Although wild-type mice did not alter their burying response to stress-provoking marbles after puberty, CRFR2-deficient mice showed a dramatic increase in burying behavior. We conclude that identification of abnormal pubertal stress pathway maturation may be predictive of adult heightened stress sensitivity and future susceptibility to stress-related affective disorders.

This article has been cited by other articles:

				N. Goel and T. L. Bale Organizational and Activational Effects of Testosterone on Masculinization of Female Physiological and Behavioral Stress Responses Endocrinology, December 1, 2008; 149(12): 6399 - 6405. [Abstract] [Full Text] [PDF]

				J. B. Becker, L. M. Monteggia, T. S. Perrot-Sinal, R. D. Romeo, J. R. Taylor, R. Yehuda, and T. L. Bale Stress and Disease: Is Being Female a Predisposing Factor? J. Neurosci., October 31, 2007; 27(44): 11851 - 11855. [Full Text] [PDF]