DPP4-deficient congenic rats display blunted stress, improved fear extinction and increased central NPY

Journal article


Publication Details

Author(s): Canneva F, Golub Y, Distler J, Dobner J, Meyer SK, von Hörsten S
Journal: Psychoneuroendocrinology
Publication year: 2015
Volume: 53
Pages range: 195-206
ISSN: 0306-4530


Abstract


Inhibitors of dipeptidyl peptidase 4 (DPP4, CD26) are used for the treatment of type 2 diabetic patients and better glucose tolerance has been confirmed in functionally DPP4-deficient congenic rats (DPP4mut), along with immunological alterations and, interestingly, a stress-resilient phenotype. All these findings are in agreement with the "moonlighting" properties of DPP4, whose proteolytic action is responsible for the inactivation of a number of regulatory peptides including, but not limited to, neuropeptide Y (NPY). Among all candidate substrates, DPP4 displays highest affinity for NPY, an endogenous anxiolytic neurotransmitter that is suggested as a candidate biomarker in post-traumatic stress disorder (PTSD) and depression.Central and peripheral NPY levels were measured by ELISA in DPP4mut and DAwt rats revealing a significantly higher concentration of the peptide in the CSF of DPP4mut animals. This finding positively correlated with the blunted stress phenotype measured on an analgesia-meter. Additionally, when a classical fear-conditioning paradigm was investigated, short-term fear extinction was significantly potentiated in DPP4mut rats as compared to wt controls.Our findings indicate a positive correlation between reduced stress-responsiveness and increased central NPY, in DPP4mut rats. Most interestingly, the behavioral phenotype extends to facilitation of fear extinction. These observations raise further interest in DPP4-modulating drugs for the potential effect on NPY metabolism, as a therapeutic tool for psychiatric conditions such as anxiety disorders and PTSD.



FAU Authors / FAU Editors

Distler, Jörg PD Dr.
Heisenberg-Professur für Molekulare Mechanismen der Organfibrose
Golub, Yulia PD Dr.
Kinder- und Jugendabteilung für Psychische Gesundheit in der Psychiatrischen und Psychotherapeutischen Klinik
Meyer, Sarah Katharina
Medizinische Fakultät
von Hörsten, Stephan Prof. Dr.
Professur für Experimentelle Biomedizin


How to cite

APA:
Canneva, F., Golub, Y., Distler, J., Dobner, J., Meyer, S.K., & von Hörsten, S. (2015). DPP4-deficient congenic rats display blunted stress, improved fear extinction and increased central NPY. Psychoneuroendocrinology, 53, 195-206. https://dx.doi.org/10.1016/j.psyneuen.2015.01.007

MLA:
Canneva, Fabio, et al. "DPP4-deficient congenic rats display blunted stress, improved fear extinction and increased central NPY." Psychoneuroendocrinology 53 (2015): 195-206.

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Last updated on 2019-20-07 at 07:14