Effects of tacrolimus on c-fos in hippocampus and memory performances in streptozotocin model of Alzheimer’s disease of rats

Abstract

IntroductionAlzheimer's disease (AD), the most common dementia in older population is a progressive neurodegenerative age-related disease. The frequency of this disease is 0.1% between 60 and 65 ages and increases logarithmically up to 48% over age of 85. Considering that, by 2050, 25% of the world's population will be over 65; AD will be the most important health problem on the top [1]. There is no promising cure yet in fact the main factor that lies under the mechanism to cause the defects is not even known for certain. However, we know that the most important defect of this disease is the debates which appears as a form of amyloid beta (Aβ) plaque accumulation [2]. These plaques later become a slayer for the neuron itself. It is not accurate to label the pathway either as apoptosis or as necrosis, which is another fact to discuss [3]. However, it is certain that significant amount of neuron dies through this process. Another known defect is the tau neurofibrillary tangles, which occur between the neurons and in later on interrupts the communication between each of them. Without communication and nutrition, neurons begin to die and soon cell reduction happens. As time progresses more the Aβ plaques accumulate more debits surrounds the brain. Patients usually die of aspiration pneumonia about 9 years after disease onset [4].Different drugs are used for AD treatment, but they can only slow the decline of the diseases' progression. A class of a pharmacotherapy which contains cholinesterase Background/aim: Calcineurin, an inhibitor of calcium dependent phosphatase is highly presented in a brain of an Alzheimer's disease. Aging brain gets more sensitive to hyperactivation of calcineurin, and this event causes tau neurofibrillary plaque accumulation, which is one of the outcomes of this disease. The regions of hippocampus are much effected from the results of this process. Our hypothesis is that a calcineurin inhibitor, tacrolimus, could prevent the accumulation and the decrease of the neuronal cells. Therefore, this immunosuppressive drug could be a candidate for an early treatment of Alzheimer disease. Materials and methods:Fifteen male Wistar albino rats were divided to three groups; control, Alzheimer, and Alzheimer+Tacrolimus. The Alzheimer group received an injection of streptozotocin intracerebroventricularly for the purpose of modelling the disease via generating free radicals leading a cognitive impairment. Alzheimer+Tacrolimus group first received an oral drug, a calcineurin inhibitor for 10 days afterwards prepared for the model as same as the Alzheimer group received. Finally, all groups performed the Morris water maze test for four days then sacrificed. For the aim of counting neurons in the hippocampus stereological methods, as well as for an evaluation of cellular response to stress in dentate gyrus, a c-Fos immunohistochemistry was performed.Results: According to the probe trial of Morris water maze test, the latency time was dramatically higher at both Alzheimer and Alzheimer+Tacrolimus group (p < 0....

Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer’s Disease

“…In the same study, the administration of FK506 to APP-KI mice also significantly restored hippocampal LTP, without altering LTP, in wild-type mice [157]. However, a recent study using tacrolimus in rats treated with streptozotocin did not show any preventive effects on neuronal loss [359].…”