| Background: Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Up to date, the etiology and pathogenesis of AD are completely unclear, and its treatme -nt is mainly symptomatic. Senile plaques, a key pathological feature of AD, are essentially composed of the amyloid–beta (Aβ) peptide. Aβaccumulation in the brain is the primary influence driving the pathogenesis of AD. Therefore, targeting of cerebral Aβin all its aggregation forms has been suggested for therapeutic purposes of the disease. Evidence has emerged that the residues 3-6 (EFRH) of Aβ1-10 has been implicated in its self-aggregation. In our previous study, a peptide specifically binding to Aβ1-10 had been identified by phages displaying technology, and its inhibitory effect on Aβaggregation and toxicity had been confirmed in vitro. In order to further confirm wether the peptide had the similar anti- Aβeffect in vivo, we explored its effects on behavior and pathology in AD model rats in this study.Objective: To investigate effects of the specific peptide binding to Aβ1-10 on behavior and pathological changes in AD model rats induced by Aβ1-42.Methods: SD rats were randomly divided into control group, model group, treatment group (further divided into small-dose group, middle-dose group and high-dose group). Through one side of the intracerebroventricular injection, model group and treatment group were both injected with Aβ1-42, treatment group with the oligopeptide and control group with normal saline for 14 consecutive days. Morris task and open field test were used to test the behavioral performance, and HE, congo red and immunohistochemical staining were employed to observe on pathological changes in rats. All the data was analysed by the SPSS 17.0 software, and parts of the plans were drawn by the Origin 7.5 software.Results:1. Behavioral performanceMorris water maze: In the place learning: The latency and swimming distance decreased with days (Ps< 0.01), and these indices in the middle-dose group were significantly short compared to the model group (Ps< 0.05). In the probe trial: the percentage of swimming distance in the target quadrant in the middle-dose group was significantly longer than that in the model group (P< 0.05), and similar to the control group.Open field test: There was insignificant difference in the latency, squares crossed, and peripheral time among groups (Ps >0.05).2. Pathological test: After HE staining, Aβwas stained to uniform and light pink. The pyramidal cell layers in the hippocampal CA1 were partly observed under the light microscope. Moreover, glial cell proliferation could be observed around necrotic neurons. Senile plaques could be seen in the frontal, parietal of rat brain tissue both in the model group and treatment group, but they was few, small patches and light staining in the middle-dose group compared to the model group via Congo red and immunohistochemical staining.Conclusion: In vivo, appropriate dose of the oligopeptide could not only improve spatial learning and memory, but reduce the pathological changes of AD in rats.
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