@article{N_Kn_A_D_P_2016, title={PHOSPHORYLATION OF TAU PROTEIN IN BRAIN REGIONS OF CHRONIC RENAL FAILURE - INDUCED RATS: AMELIORATIVE EFFECT OF ERYTHROPOIETIN}, volume={9}, url={https://journals.innovareacademics.in/index.php/ajpcr/article/view/11652}, abstractNote={<p>Objectives: Chronic kidney disease (CKD) is a major clinical health problem as it is a systemic disorder that causes widespread organ damage<br />and it is related to significant morbidity and mortality. Numerous studies have shown that, cognitive dysfunction increase in prevalence, due to<br />increase in reactive oxygen species in CKD severity. Tau proteins are proteins that stabilize microtubules. Hyperphosphorylation of tau reduces its<br />ability to bind to microtubule causes dystabilization and production of neurofibrillary tangles (NFT) and neurodegeneration in the brain. Aberrant<br />hyperphosphorylation of tau is critical to the progression of neurodegeneration. Erythropoietin (EPO), a glycoprotein has been in clinical use for<br />millions of anemic patients, and some studies show it has a neuroprotective role. Till now studies on the level of tau protein phosphorylation in brain<br />regions of CKD-induced experimental animals and impact of EPO therapy are scarce. The aim of this study is to determine the impact of CKD and EPO<br />therapy on tau protein phosphorylation in brain regions of experimental rats.<br />Methods: This study was performed on 48 adult male Wistar rats. Two phases were conducted to find out the difference between simultaneous and<br />posttreatment of EPO. Phase I: 24 adult male Wistar rats were divided into 4 groups (6 animals each): Group 1: Control, Group 2: 0.75% of adenine<br />mixed diet for 4 weeks, Group 3: 0.75% of adenine mixed diet was given for 4 weeks and simultaneous administration of EPO (100 IU/kg btw, ip)<br />thrice weekly. Group 4: EPO alone (100 IU/Kg btw, ip) thrice per week. All the animals were sacrificed uniformly at the end of 4 weeks. In Phase II,<br />24 animals were maintained separately for 40 days experimental period and divided into 4 groups. Groups 1, 2, and 4 animals were treated as same<br />mentioned in Phase I. Group 3: For EPO posttreatment, adenine mixed diet was given for 4 weeks for chronic renal failure (CRF) induction. After the 4</p><p>week, EPO (100 IU/Kg btw.) was administered daily once for 12 days. At the end of the 40 days, all the animals were sacrificed uniformly. In both the<br />phases after the treatment period, the brain tissue was removed and samples were homogenized. Total tau protein and phosphorylated tau protein<br />expressions were analyzed by western blotting method.<br />Results: In results, both the total tau and phosphorylated tau protein levels were significantly increased all the brain regions of CRF-induced groups<br />when compared to control. In both simultaneous and posttreatment of EPO, the levels were retrieved.<br />Conclusion: This study proves that EPO supplementation has a promising role in neuroprotection by preventing abnormal phosphorylated tau<br />protein accumulation. This study also proves the clinical usefulness of EPO as a supplemental therapeutic agent in neurotoxicity.<br />Keywords: Chronic renal failure, Cognitive dysfunction, Hyperphosphorylation of tau protein, Erythropoietin.<br />th</p>}, number={3}, journal={Asian Journal of Pharmaceutical and Clinical Research}, author={N, KARTHICK and Kn, Poornima and A, Saravanan and D, Alwin and P, Venkataraman}, year={2016}, month={May}, pages={392–397} }