en Behavioral Neuroscience Behavioral Neuroscience Original Original <strong>Objective:</strong> Hypoxia via expression of Hypoxia Inducible Factor-1 (HIF-1) is an important and effective factor in the onset and progression of memory disorders such as Alzheimer Disease (AD). The activity of &beta;-secretase (BACE1) increased in hypoxia condition. BACE1 trigger a cascade of pathological events resulting in AD. Crocin act as memory improvement agent but its molecular mechanism is not well-known. So, in this study, the effect of crocin on spatial memory, HIF-1&alpha; and BACE1 gene expression were investigated in rat offspring under maternal hypoxia.<br> <strong>Materials and methods:</strong> Female pregnant rats on the 20th day of pregnancy were divided into 4 groups including: sham, crocin treated, hypoxia and hypoxia group treated with crocin. In hypoxia groups, pregnant rats were exposed to the 7% oxygen and 93% nitrogen intensity for 3 hours. In the crocin treated group, crocin (30 mg/kg) injected at P14-28, (i.p). At the end, Morris water maze was used to assess spatial memory and Real-Time PCR analysis was performed to measure the expression of BACE1 and HIF-1&alpha; genes in the brain of offspring.<br> <strong>Results:</strong> Maternal hypoxia impaired memory task compared to the sham group. But crocin treatment improved cognitive behavior. HIF-1&alpha; and BACE1 expression were unregulated in the brain of offspring in hypoxia group. Crocin treatment could attenuate the expression of both genes<span dir="RTL">.</span><br> <strong>Conclusion:</strong> According to our results, down- regulation of HIF-1&alpha; and BACE1 gene expression in the brain of rat offspring after crocin treatment can be suggested as molecular mechanism for crocin to improve spatial memory. Maternal hypoxia, Spatial memory, Rat offspring, Crocin, HIF1, BACE1 499 506 http://bcn.iums.ac.ir/browse.php?a_code=A-10-1787-1&slc_lang=en&sid=1 Fahimeh Fahimi Truski fahimeh.fahimi.m69@gmail.com 13700319475328460029423 13700319475328460029423 No Department of Physiology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran. Zohreh Ghotbeddin z.ghotbeddin@scu.ac.ir 13700319475328460029424 13700319475328460029424 Yes Department of Physiology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran. Mohammad Reza Tabandeh m.tabandeh@scu.ac.ir 13700319475328460029425 13700319475328460029425 No Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran. Mahdi Pourmahdi Borujeni pourmahdim@scu.ac.ir 13700319475328460029426 13700319475328460029426 No Department of Food Hygiene, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran