Changes in Gene Expression Profiles in Adult Rat Brain Structures after Neonatal Action of Dipeptidyl Peptidase-IV Inhibitors

Abstract

Background: Previous studies have shown the development of emotional and motivational disorders, such as anxiety-depression-like disorders with increased aggression in adolescent and adult Wistar rats, occurs after neonatal exposure to the dipeptidyl peptidase-IV (DPP-IV, EC 3.4.14.5) inhibitors diprotin A and sitagliptin (postnatal days 5–18). Methods: In this study, using real-time PCR, we evaluated changes in the gene expression of serine protease DPP-IV and prolyl endopeptidase (PREP, EC 3.4.21.26; dpp4 and prep genes), monoamine oxidase А (maoA) and B (maoB), and serotonin transporter (SERT; sert) in the brain structures from 3-month-old rats after postnatal action of DPP-IV inhibitors diprotin A and sitagliptin. Results: Dpp4, sert, and maoB gene expression increased and maoA gene expression changed with a tendency to increase in the striatum of rats with neonatal sitagliptin action. The increase of maoA gene expression was also shown in the amygdala. An increase in prep gene expression was found in the striatum of rats with the neonatal action of diprotin A, and a decrease in maoB gene expression was observed in the amygdala. We detected a significant downward trend in sert gene expression in the frontal cortex and amygdala, as well as a tendency to increase in maoA gene expression in the hypothalamus. Discussion: These findings suggest that changes in the expression of the abovementioned genes are associated with the development of anxiety and depression, with increased aggression caused by the neonatal action of diprotin A and sitagliptin.

Long-Term Social Isolation Reduces Expression of the BDNF Precursor and Prolyl Endopeptidase in the Rat Brain

“…These rats demonstrated slower learning in the active avoidance test than the control group animals [37]. The anxiety depres sive state induced by another inhibitor of dipeptidyl pep tidase IV was accompanied by the upregulation of the prep gene expression in the STR [38]. An increase in the PREP activity in the FC and HPC of male Wistar rats was observed in the model of experimental retrograde amne sia induced by the m cholinoblocker scopolamine (mus carinic receptor antagonist) or by the maximal elec troshock [39].…”