en Related Fields Related Fields مقاله کامل Full Length/Original Article <strong>Background:</strong> Matrix metalloproteinase-9 (MMP-9) expression has been implicated in molecular mechanisms of neurodegenerative disorders, and its abnormal level has been reported in Alzheimer&rsquo;s disease (AD). Some protective mechanisms of statins against neurodegeneration might be mediated by the inhibition of MMP-9 expression. Here, we investigated the effect of simvastatin, on the hippocampal MMP-9 expression in the context of AD. <strong>Methods:</strong> We examined the influence of three-week simvastatin (5 mg/kg) administration on hippocampal MMP-9 expression in a rat model of cognitive decline induced by streptozotocin (STZ). Spatial long-term memory and MMP-9 expression were assessed by Morris&nbsp;water&nbsp;maze (MWM) test and quantitative polymerase chain reaction, respectively. <strong>Results:</strong> The results showed a decline in the learning and memory in STZ group when compared with the control group. The MMP-9 was up-regulated (1.41 &plusmn; 0.2 vs. 0.980 &plusmn; 0.02, <em>p</em> < 0.05), and cresyl violet staining showed hippocampal cell damage in STZ group compared with the control group. Simvastatin prevented the up-regulation of MMP-9 (1.05 &plusmn; 0.05 vs. 1.41 &plusmn; 0.2, <em>p</em> < 0.05), improved spatial memory impairment and attenuated hippocampal cell damage. Furthermore, we found a negative correlation (r = 0.77) between MMP-9 expression and cognitive function. <strong>Conclusion:</strong> Our findings suggest that the neuroprotective influence of simvastatin in battle to cognitive impairment is mediated in part by the modulation of MMP-9 expression. The reduction of MMP-9 expression in simvastatin-treated animals is in correlation with the improvement of cognitive functions. Understanding the protective mechanism of simvastatin will shed light on more efficient therapeutic modalities in AD. Alzheimer’s disease, Matrix metalloproteinase-9, Simvastatin 262 271 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-1-748&slc_lang=en&sid=1 Soheila Adeli 0000-0002-3341-7270 No Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran Maryam Zahmatkesh 0000-0002-8950-893X Yes Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran Mitra Ansari Dezfouli No Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran