How does neurokinin 3 receptor agonism affect pathological and cognitive impairments in an Alzheimer's disease-like rat model?

Alzheimer's disease (AD) is accepted as a form of progressive dementia. Cholinergic systems are commonly affected in AD. Neurokinin 3 receptor (NK3R) is involved in learning memory-related processes. It is known that the activation of NK3R affects the release of many neurotransmitters. The aim of this project was to investigate the effects of NK3R agonist senktide administration on neurobehavioral mechanisms in the experimental AD-like rat model. 50 male Wistar albino rats were divided into Control (C), AD, Control + NK3R agonist (CS), AD + NK3R agonist (ADS), AD + NK3Ragonist + antagonist groups (ADSO). We designed AD-like model by intrahippocampal administration of Aß1-42. After NK3R agonist + antagonist injections, open field (OF), Morris water maze (MWM) tests were applied. Cholinergic mechanism analysis from hippocampus-cortex tissues was performed by ELISA and catecholamine analysis from brain stem tissue were performed by HPLC method. The transitions from edge to center, rearing, grooming parameters were found to be reduced in final values of OF. While the group-time interaction was significant in the OF test findings, there was no significant difference between the groups. In MWM test, ADS group showed a learning level close to control group and animals in AD and ADSO groups could not learn target quadrant in MWM test. The brain stem NA and DA concentrations were not statistically significant. Hippocampal AChE-ChAT levels were supported by positive effects of senktide on learning via the cholinergic mechanisms. As a result, NK3R agonists were found to be effective in improving cognitive functions in rats with AD pathology. In the experimental AD model, positive effects of NK3R on learning memory may be mediated by cholinergic mechanisms.

Does Sertraline Affect Hypothalamic Food Intake Peptides in the Rat Experimental Model of Chronic Mild Stress-Induced Depression?

Depression is a chronic, recurrent and life-threatening disease affecting approximately 15% of the world population. Depression is responsible for neuropathologies like decreased neurogenesis and increased dendritic atrophy. Antidepressant treatments increase hippocampal neurogenesis and neurotrophic factor expression. Based on this information, it was aimed to investigate effect of sertraline on depression in rats with chronic mild stress (CMS) model and to determine how it affects cell proliferation and hypothalamic peptide levels in hypothalamus. 56 adult male Wistar albino; control, depression(D), depression + sertraline, sertraline were divided into groups. Various stressors were applied to D for 30 days. Open field test (OFT) and forced swimming test (FST) were conducted to check whether the animals were depressed. On the 16th day osmotic minipump was placed subcutaneously and sertraline (10 mg/kg/day) was administered for 15 days. Behavior tests were done. Hypothalamic peptide gene expression levels were analyzed by quantitative RT-PCR. Statistical evaluations were made using ANOVA. It caused a decrease in the percentage of movement in the D and control groups in the OFT, an increase in the immobility time in the D group in the FST, and an increase in the swimming behavior in the DS group. Animals did not show any anxiological behavior based on the elevated plus maze test results. CMS caused a decrease in GLUT2 and NPY gene expression in the hypothalamus of animals, an increase in POMC and FGFR2, and an increase in IGFIR and GLUT2 gene expression in the DS group. Sertraline has been shown to ameliorate the effects of CMS-induced depression. Sertraline is thought to have a positive regulatory effect on both the formation of neural precursor cells and the survival of newly formed neurons in the hypothalamus. Newly formed neurons in the hypothalamus express food intake-related NPY, POMC, GLUT2 neurons, and thus hypothalamic tanycytes may play a key role in the control of energy metabolism.

Effects of Combined Sertraline and Magnesium in Rat Atrium.

The objective of this study is to determine the synergistic effects of an antioxidant ion Mg+2, combined with selective serotonin reuptake inhibitor sertraline, in treatment or prevention of major depression and regulation of inotropic effect in the early postoperative period. Adult male 40 Wistar albino rats were randomly divided into 6 groups. Three to 4-mm long atrium strips were placed in organ bath, tension was adjusted to 2 g. Isometric contractions were induced with 10-3 M adrenaline. Group 1 was the control group, cumulative sertraline was given to group 2, cumulative MgSO4 to group 3, combined cumulative sertraline and MgSO4 to group 4, intraperitoneal sertraline injection for 29 days to group 5, and intraperitoneal MgSO4 injection for 14 days to group 6. Changes in weight, tensions, bleeding/clotting time, and biochemical findings were evaluated statistically. Isometric tension relationship between groups 1 and 3 was statistically significant after 4 mmol/L MgSO4 (p < 0.05). A rapid inhibition of contraction was observed in group 4. Inhibition of spontaneous contractions of groups 5 and 6 was found to be statistically significant at close values, p < 0.05. When blood clotting times were compared, a statistically marked decrease was found in group 6, p < 0.05. Compared to control group, there was a significant decrease in blood lipids in group 4. While LDH and CK-MB increased from plasma enzymes in groups 5 and 6, no significant change was observed in NT-proBNP. Combined treatment of high dose MgSO4 with antidepressants for pre or post-operative depression may cause fatal risks. Shortening clotting time may increase the risk of embolism and stroke. In order to reduce the risk of post-operative depression preoperatively, care should be taken when using magnesium combined with antidepressants and more studies are needed to be considered.