Investi̇gati̇on of the fez1 gene expressi̇on and the role of pi̇nealectomy on the pathogenesi̇s of alzhei̇mer produced experi̇mentally i̇n rats

Investigation of the FEZ1 gene expression and the role of pinealectomy on the pathogenesis of Alzheimer produced experimentally in rats Aim: The Alzheimer Disease (AD) is a neuro-degenerative brain disease that has a specific pathology such as the formation of senile plaque, neurofibrillary tangles, and clinical symptoms such as memory loss, decrease in intellectual functions and failures in cognitive functions. Immunohistochemical studies have shown that many neurologic diseases, including mental diseases, develop due to neocortex dysfunction, and these diseases may be related with the FEZ1 (Fasciculation and Elongation Protein Zeta-1) expressed in the deeper layers of the neocortex. This study was designed to determine the possible relation between the AD and FEZ1 and the neurotransmitters (serotonin, noradrenaline, dopamine) and melatonin have an important role in axonal transfer and regulating the controlled balance of the excitator/inhibitor signals. Material and Method: 60 male rats weighing 220-280 gr will be used in the study. The rats were divided into 6 groups (n= 10), which are: sham intra-cerebro-ventricular (ICV) control, sham ICV+Pinealectomy (PnX)+intraperitoneal (i.p.) control, streptozotocin (STZ), Melatonin+STZ, PnX+STZ and Melatonin+STZ+PnX group.The Morris water tank tests was applied to all animals for 5 days (between the 3-7. days, 4 recurrences), and the scores were analyzed with a software program ((EthoVision XT10 Image Analysis). On the 8th day, the PnX and ICV applications were start. The ICV STZ injections were applied to the rats on the 8th and 10th days as 3 mg/kg. The PnX process was applied to the rats before the STZ application. Melatonin applications (as i.p. 10 mg/kg/day) were started 1 hour before the first dose of STZ application, and was continued for 14 days. 14 days after the first STZ application, the behavioral tests were applied for 5 days, again.In the end of behavioral tests, the rats were sacrified and their blood and hippocampus tissues were collected. The serum serotonin, noradrenaline and dopamine levels were determined with the ELISA (Enzyme-linked immuno sorbent assay) method. The hippocampus area from the brain will be divided into two portions. The FEZ1 gene expression were determined with PCR (Polymerase Chain Reaction) and protein levels of FEZ1 were measured via Western Blot method. Results: In the ICV STZ group, the levels of FEZ1 were found higher than both sham groups (p<0.05). While the levels of FEZ1 in the ICV STZ+MLT group were similar to sham groups, the levels of FEZ1 in the ICV STZ+PnX+MLT group were found to be lower than ICV STZ+PnX and even sham groups (p<0.05). While no statistically significant differences were observed between the groups in terms of serum dopamine and serotonin levels, the noradrenaline levels of all experiment groups were found to be lower than that of sham groups (p<0.05). Conclusion: Study results demonstrated that FEZ1 levels were to be high in the rat models of Alzheimer's Disease and these inreases in FEZ1 levels were turned back by melatonin. Keywords: FEZ1, Alzheimer's disease, pinealectomy, melatonin, serotonin, dopamine, noradrenaline, rat