Crocin Treatment after Maternal Hypoxia Attenuates Spatial Memory Impairment and Expression of BACE1 and HIF-1α in Rat Offspring Brain

Introduction: 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 β-secretase (BACE1) is increased in hypoxia conditions. BACE1 triggers a cascade of pathological events resulting in AD. Crocin acts as a memory-improving agent but its molecular mechanism is not well-known. Therefore, in this study, the effect of crocin on spatial memory, HIF-1α, and BACE1 gene expression was investigated in rat offspring under maternal hypoxia. Methods: 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 the hypoxia groups, pregnant rats were exposed to 7% oxygen and 93% nitrogen intensity for 3 h. In the crocin-treated group, crocin (30 mg/kg) was injected at P14-28 (i.p). At the end, Morris water maze was used to assess spatial memory and real-time polymerase chain reaction was performed to measure the expression of BACE1 and HIF-1α genes in the brain of offspring. Results: Maternal hypoxia impaired memory compared with the sham group. However, crocin treatment improved cognitive behavior. HIF-1α and BACE1 expressions were upregulated in the brain of offspring in the hypoxia group. Crocin treatment could attenuate the expression of both genes. Conclusion: According to our results, down-regulation of HIF-1α and BACE1 gene expressions in the brain of rat offspring after crocin treatment can be suggested as a molecular mechanism for crocin to improve spatial memory.