The effect of neuropeptide Y1 receptor agonist on hypothalamic neurogenesis in rat experimental depression model

Depression is responsible for neuropathies such as decreased neurogenesis and increased dendritic atrophy. There is information that antidepressant treatments have an effect by increasing hippocampal neurogenesis and neurotrophic factor expression. The neuropeptide Y1 (NPY1R) receptor agonist has been suggested to have anxiolytic effects. Based on this information, it was aimed to investigate the effect of NPY1R agonist on depression in rats with depression using the CMS model and to determine how depression affects cell proliferation in the hypothalamus and hypothalamic peptide levels. Forty-eight adult, male Wistar albino rats were divided into groups as Control, Depression (D), Depression + NPY1R and NPY1R. Various stressors were applied to D for 30 days. An open field test (OFT) and forced swim test (FST) were performed to check whether the animals were depressed. On the 16th day, an osmotic mini pump was placed under the skin and NPY1R (130 ul/kg/day) was applied for 15 days. Behavioral tests were performed, hypothalamic peptide gene expression levels were analyzed by quantitative RT-PCR and statistical evaluations were made using ANOVA. A decrease in the percentage of movement in the D and control groups were noted in the OFT, an increase in the immobility time in the D group in the FST, and an increase in swimming behavior in the DNPY1R group. The animals did not display any anxiety behavior based on the elevated plus maze test results. It caused a decrease in IGF1R, FGF2, POMC, NPY and GLUT2 gene expression in the hypothalamus of depression group animals, and an increase in NPY gene expression in NPY1R treatment. This study compellingly demonstrated that exposure to chronic mild stress simultaneously downregulates gene expression in the hypothalamus; we observed that NPY receptor NPY1R treatment increased the effect of NPY. Therefore, adjunctive treatments with appropriate molecules such as NPY, Y1 receptor agonists or pharmacological derivatives may have significant potential in the treatment of depression.