Effect Of Calcineurin On Learning And Memory And Related Mechanism In Aβ1-42-Induced Ad Rats

Objective This study was designed to investigate the calcineurin effect on learning and memory and expression of synaptic proteins and metalloproteinase-9 in Aβ1-42-induced Alzheimer model rats.Methods Thirty-six Sprague-Dawley rats were randomly divided into 3 groups (AD group, FK506 group and control group). AD group and FK506 group were given Aβ1-42 intra-hippocampal bilaterally injection to build AD model, while the control group was given PBS relatively. FK506 group were given injection of 0.2% FK506 (0.2mg/100g, intraperitoneal), AD group and the control group received saline (0.2mg/100g, intraperitoneal). The learning and memory ability of rats was tested using a Morris water maze. The gene expression of MMP-9、PSD-95 and Homer、Shank gene subtypes in hippocampus region were analyzed by semiquantitative RT-PCR. The protein level of metalloproteinase-9 (MMP-9) was quantified by immunohistochemistry, and quantitative measurement of activity expression of MMP-9 was analyzed by gelatin zymography.Result Compared to the control group, the learning and memory ability was obviously decreased in AD model rats (P＜0.01), and the gene expression of PSD-95、Homer1b、Shank1、Shank3 were reduced, the expression of Homer1a was raised (P<0.05). Compared to AD group, after FK506 treatment, the learning and memory ability was improved (P<0.01), and the gene expression of PSD-95、Homer1b、Shank1、Shank3 were raised (P＜0.05), but the expression of Homer1a was lowered (P<0.01). The mRNA expression of Shank2 had no significant difference between the three groups. Compared with the control groups, the mRNA and protein expression levels of MMP-9 were significantly increased in AD groups (P<0.05). Fk506 can reduced MMP-9 mRNA expression significantly compared to AD groups (P<0.05), and quantitative measurement of activity expression of MMP-9 by Gelatin zymography analysis revealed the similar results, respectively (P<0.05).Conclusions Inhibiting Calcineurin can obviously heighten the synaptic related proteins in gene expression levels, which affects axonal function and plasticity. Inhibiting calcineurin may influence the expression of MMP-9, thus alleviate the AD symptom.