Effects of kisspeptin and aromatase inhibition on cognitive functions and behavior in female rats

Effects of Kisspeptin and Aromatase Inhibition on Cognitive Functions and Behavior in Female RatsKisspeptin (encoded by KiSS-1 gene) is a neuropeptide in various brain regions, especially in the hypothalamus. Expressions of this kisspeptin and its receptor (GPR54) have been shown in other brain areas such as hippocampus and cortex. However, function of kisspeptin/GPR54 system in the hippocampus has not been studied using in vivo models. Therefore, in this project, effects of kisspeptin and letrozol on learning, memory, animal activity (motor functions), depression and anxiety behavior and their underlying mechanisms were investigated. Kisspeptin's neuronal activity is modulated by estrogen. Therefore, in this experimental model an aromatase inhibitor (letrozole) was used to block synthesis of this steroid hormone. Adult female Sprague/Dawley rats were allocated in four groups: Control, kisspeptin (10 nmol/ day), letrozole (1 mg/kg oral) and kisspeptin + letrozole. Alzet mini osmotic pump and ICV infusion kits were inserted by using a stereotaxic frame under anesthesia. Drugs were infused for 28 days. Cognitive functions (Morris Water Maze), animal activity (open field and beam tests), depression (tail suspension test) and anxiety (dark/light test) behavior were determined before and at the end of experiments. Experiments were ended by decapitation and blood samples obtained. Serum estradiol levels were determined by ELISA method. Frozen brain sections were cut on cryostat. Number of neurons, changes in Erk 1/2 pathways and PSD-95 and Synaptophysin protein expression were determined by cresyl violet staining, Western blotting in hippocampus, sensory-motor cortex. Data were statistically analyzed by using One-Way ANOVA. Phosphorylated ERK-2 protein levels were significantly increased in the test groups compared to the control values (p < 0.05). Locomotor activity of the animals in the kisspeptin + letrozol group was significantly increased compared to the letrozol infused group alone (p<0.05). In conclusion, kisspeptin / GPR54 system may affect learning and memory through Erk-2 pathway. However, kisspeptin's effects on cognitive functions may be further elucidated by using different dose groups and/or memory deficit induced animal models. Key Words: Anxiety and depression behavior, Kisspeptin, Letrozole, learning and memory, estrogen