Role of hypothalamus-pituitary-adrenal axis modulation in the stress-resilient phenotype of DPP4-deficient rats

Golub Y, Schildbach EM, Touma C, Kratz O, Moll G, von Hörsten S, Canneva F (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Behavioural Brain Research Elsevier

Book Volume: 356

Pages Range: 243-249

DOI: 10.1016/j.bbr.2018.08.029

Abstract

BACKGROUND: Dipeptidyl peptidase 4 (DPP4, CD26) is a moonlighting enzyme responsible for the proteolytic inactivation of neuropeptide Y (NPY), a peptide known for its anxiolytic effect in the central nervous system. Our previous work revealed a stress-resilient phenotype and a potentiation of short-term fear extinction in a congenic rat model deficient for DPP4 activity (DPP4mut). Here, we investigated neuroendocrine mechanisms underlying the phenotype of the DPP4mut animals. We studied the function of the hypothalamus-pituitary-adrenal (HPA) axis including the expression levels of its key genes and explored the possibility of structural NPY system changes. METHODS AND RESULTS: We find decreased expression of Nr3c1 (glucocorticoid receptor - GR) and Fkbp5 (FK506 binding protein 5) in the amygdala and the hypothalamus of the DPP4mut rats, as well as the lower stress-induced peripheral corticosterone (CORT) levels. We detect no significant alterations in basal and DEX-induced CORT levels in the DPP4mut animals. The abundance of NPY-ergic neurons in the basolateral amygdala, dentate gyrus and hippocampus did not differ between the DPP4mut and their wild type littermates. CONCLUSION: DPP4mut rats show blunted CORT response in line with their lower behavioral stress-response profile. These results are consistent with the hypothesis that increased central NPY levels elevate the threshold of stress response. We suggest that changes in the expression levels of key HPA axis genes (Nr3c1 and Fkbp5) are a consequence of the altered stress-perception of DPP4mut animals, thus further contributing to the stress-resilient phenotype.

Authors with CRIS profile

Yulia Golub Department of Child and Adolescent Mental Health Oliver Kratz Department of Child and Adolescent Mental Health Stephan von Hörsten Professur für Experimentelle Biomedizin

Involved external institutions

Universität Osnabrück DE Germany (DE)

How to cite

APA:

Golub, Y., Schildbach, E.-M., Touma, C., Kratz, O., Moll, G., von Hörsten, S., & Canneva, F. (2019). Role of hypothalamus-pituitary-adrenal axis modulation in the stress-resilient phenotype of DPP4-deficient rats. Behavioural Brain Research, 356, 243-249. https://doi.org/10.1016/j.bbr.2018.08.029

MLA:

Golub, Yulia, et al. "Role of hypothalamus-pituitary-adrenal axis modulation in the stress-resilient phenotype of DPP4-deficient rats." Behavioural Brain Research 356 (2019): 243-249.

BibTeX: Download